Connecting European Neuroscience

EJN Table of Content

Wiley: European Journal of Neuroscience: Table of Contents Table of Contents for European Journal of Neuroscience. List of articles from both the latest and EarlyView issues. https://onlinelibrary.wiley.com/journal/14609568?af=R Wiley: European Journal of Neuroscience: Table of Contents Wiley en-US European Journal of Neuroscience European Journal of Neuroscience https://onlinelibrary.wiley.com/pb-assets/journal-banners/14609568.jpg https://onlinelibrary.wiley.com/journal/14609568?af=R Electrical stimulation of human corticospinal axons at the level of the lumbar spinal segments Electrical stimulation over the first lumbar spinous process (LS) delivered prior to transcranial magnetic stimulation (TMS), resulted in the occlusion of TMS evoked responses. When LS and TMS were delivered individually, respective responses showed similar increasing behaviour in relation to increasing contraction strength. These results suggest that LS activates some of the same corticospinal axons as TMS and can be used to assess the subcortical contribution to the corticospinal response. Abstract Electrical stimulation over the mastoids or thoracic spinous processes has been used to assess subcortical contribution to corticospinal excitability, but responses are difficult to evoke in the resting lower limbs or are limited to only a few muscle groups. This might be mitigated by delivering the stimuli lower on the spinal column, where the descending tracts contain a greater relative density of motoneurons projecting to lower limb muscles. We investigated activation of the corticospinal axons innervating tibialis anterior (TA) and rectus femoris (RF) by applying a single electrical stimulus over the first lumbar spinous process (LS). LS was paired with transcranial magnetic stimulation (TMS) at interstimulus intervals (ISIs) of −16 (TMS before LS) to 14 ms (LS before TMS). The relationship between muscle contraction strength (10%–100% maximal) and the amplitude of single‐pulse TMS and LS responses was also investigated. Compared to the responses to TMS alone, responses to paired stimulation were significantly occluded in both muscles for ISIs ≥−8 ms (p ≤ 0.035), consistent with collision of descending volleys from TMS with antidromic volleys originating from LS. This suggests that TMS and LS activate some of the same corticospinal axons. Additionally, the amplitude of TMS and LS responses increased with increasing contraction strengths with no change in onset latency, suggesting responses to LS are evoked transsynaptically and have a monosynaptic component. Taken together, these experiments provide evidence that LS is an alternative method that could be used to discern segmental changes in the corticospinal tract when targeting lower limb muscles. Jakob Škarabot, Paul Ansdell, Callum G. Brownstein, Kevin Thomas, Glyn Howatson, Stuart Goodall, Rade Durbaba https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14321?af=R European Journal of Neuroscience Electrical stimulation of human corticospinal axons at the level of the lumbar spinal segments

Electrical stimulation over the first lumbar spinous process (LS) delivered prior to transcranial magnetic stimulation (TMS), resulted in the occlusion of TMS evoked responses. When LS and TMS were delivered individually, respective responses showed similar increasing behaviour in relation to increasing contraction strength. These results suggest that LS activates some of the same corticospinal axons as TMS and can be used to assess the subcortical contribution to the corticospinal response.

 

Abstract

Electrical stimulation over the mastoids or thoracic spinous processes has been used to assess subcortical contribution to corticospinal excitability, but responses are difficult to evoke in the resting lower limbs or are limited to only a few muscle groups. This might be mitigated by delivering the stimuli lower on the spinal column, where the descending tracts contain a greater relative density of motoneurons projecting to lower limb muscles. We investigated activation of the corticospinal axons innervating tibialis anterior (TA) and rectus femoris (RF) by applying a single electrical stimulus over the first lumbar spinous process (LS). LS was paired with transcranial magnetic stimulation (TMS) at interstimulus intervals (ISIs) of −16 (TMS before LS) to 14 ms (LS before TMS). The relationship between muscle contraction strength (10%–100% maximal) and the amplitude of single‐pulse TMS and LS responses was also investigated. Compared to the responses to TMS alone, responses to paired stimulation were significantly occluded in both muscles for ISIs ≥−8 ms (p ≤ 0.035), consistent with collision of descending volleys from TMS with antidromic volleys originating from LS. This suggests that TMS and LS activate some of the same corticospinal axons. Additionally, the amplitude of TMS and LS responses increased with increasing contraction strengths with no change in onset latency, suggesting responses to LS are evoked transsynaptically and have a monosynaptic component. Taken together, these experiments provide evidence that LS is an alternative method that could be used to discern segmental changes in the corticospinal tract when targeting lower limb muscles.

European Journal of Neuroscience, EarlyView. Electrical stimulation of human corticospinal axons at the level of the lumbar spinal segments doi:10.1111/ejn.14321 European Journal of Neuroscience 2019-01-16T04:44:59-08:00 European Journal of Neuroscience 10.1111/ejn.14321 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14321?af=R RESEARCH REPORT Thalamic morphometric changes induced by first‐person action videogame training We investigated the impact of systematic, repeated gaming exposure to a first‐person shooter (FPS) action videogame in a sample of healthy subjects. Both cognitive and morphometric changes were found after training, including a significant long‐lasting change in posterior thalamus gray matter 3 months after exposure. The same thalamic region was identified as the best predictor of changes in gaming performance. Intensive practice with a FPS action videogame induces long‐lasting structural brain changes. Abstract Cross‐sectional data suggest videogaming as promoting modifications in perceptual and cognitive skills of players, as well as inducing structural brain changes. However, whether such changes are both possible after a systematic gaming exposure, and last beyond the training period, is not known. Here, we originally quantified immediate and long‐lasting cognitive and morphometric impact of a systematic gaming experience on a first‐person shooter (FPS) game. Thirty‐five healthy participants, assigned to a videogaming and a control group, underwent a cognitive assessment and structural magnetic resonance imaging at baseline (T0), immediately post‐gaming (T1) and after 3 months (T2). Enhancements of cognitive performance were found on perceptual and attentional measures at both T1 and T2. Morphometric analysis revealed immediate structural changes involving bilateral medial and posterior thalamic nuclei, as well as bilateral superior temporal gyrus, right precentral gyrus, and left middle occipital gyrus. Notably, significant changes in pulvinar volume were still present at T2, while a voxel‐wise regression analysis also linked baseline pulvinar volume and individual changes in gaming performance. Present findings extend over the notion that videogame playing might impact cognitive and brain functioning in a beneficial way, originally showing long‐term brain structural changes even months after gaming practice. The involvement of posterior thalamic structures highlights a potential link between FPS games and thalamo‐cortical networks related to attention mechanisms and multisensory integration processing. Davide Momi, Carmelo Smeralda, Giulia Sprugnoli, Francesco Neri, Simone Rossi, Alessandro Rossi, Giorgio Di Lorenzo, Emiliano Santarnecchi https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14272?af=R European Journal of Neuroscience Thalamic morphometric changes induced by first‐person action videogame training

We investigated the impact of systematic, repeated gaming exposure to a first‐person shooter (FPS) action videogame in a sample of healthy subjects. Both cognitive and morphometric changes were found after training, including a significant long‐lasting change in posterior thalamus gray matter 3 months after exposure. The same thalamic region was identified as the best predictor of changes in gaming performance. Intensive practice with a FPS action videogame induces long‐lasting structural brain changes.

 

Abstract

Cross‐sectional data suggest videogaming as promoting modifications in perceptual and cognitive skills of players, as well as inducing structural brain changes. However, whether such changes are both possible after a systematic gaming exposure, and last beyond the training period, is not known. Here, we originally quantified immediate and long‐lasting cognitive and morphometric impact of a systematic gaming experience on a first‐person shooter (FPS) game. Thirty‐five healthy participants, assigned to a videogaming and a control group, underwent a cognitive assessment and structural magnetic resonance imaging at baseline (T0), immediately post‐gaming (T1) and after 3 months (T2). Enhancements of cognitive performance were found on perceptual and attentional measures at both T1 and T2. Morphometric analysis revealed immediate structural changes involving bilateral medial and posterior thalamic nuclei, as well as bilateral superior temporal gyrus, right precentral gyrus, and left middle occipital gyrus. Notably, significant changes in pulvinar volume were still present at T2, while a voxel‐wise regression analysis also linked baseline pulvinar volume and individual changes in gaming performance. Present findings extend over the notion that videogame playing might impact cognitive and brain functioning in a beneficial way, originally showing long‐term brain structural changes even months after gaming practice. The involvement of posterior thalamic structures highlights a potential link between FPS games and thalamo‐cortical networks related to attention mechanisms and multisensory integration processing.

European Journal of Neuroscience, EarlyView. Thalamic morphometric changes induced by first‐person action videogame training doi:10.1111/ejn.14272 European Journal of Neuroscience 2019-01-16T04:44:24-08:00 European Journal of Neuroscience 10.1111/ejn.14272 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14272?af=R RESEARCH REPORT Expression of the axon‐guidance protein receptor Neuropilin 1 is increased in the spinal cord and decreased in muscle of a mouse model of amyotrophic lateral sclerosis The expression of the repulsive axon‐guidance protein receptor Neuropilin 1 and its main ligand Semaphorin 3A is decreased in muscle of transgenic SOD1G93A mouse model of amyotrophic lateral sclerosis, Neuropilin 1 is further increased in the spinal cord. The major repulsive axon guidance cues therefore may be increased in CNS and decreased in PNS tissue after damage. Selective inhibition of Nrp1‐regulated pathways might be a promising novel therapeutic approach for the treatment of ALS. Abstract Amyotrophic Lateral Sclerosis (ALS) is a degenerative motor neuron disorder. It is supposed that ALS is at least in part an axonopathy. Neuropilin 1 is an important receptor of the axon repellent Semaphorin 3A and a co‐receptor of vascular endothelial growth factor. It is probably involved in neuronal and axonal de‐/regeneration and might be of high relevance for ALS pathogenesis and/or disease progression. To elucidate whether the expression of either Neuropilin1 or Semaphorin3A is altered in ALS we investigated these proteins in human brain, spinal cord and muscle tissue of ALS‐patients and controls as well as transgenic SOD1G93A and control mice. Neuropilin1 and Semaphorin3A gene and protein expression were assessed by quantitative real‐time PCR (qRT‐PCR), western blot and immunohistochemistry. Groups were compared using either Student t‐test or Mann–Whitney U test. We observed a consistent increase of Neuropilin1 expression in the spinal cord and decrease of Neuropilin1 and Semaphorin3A in muscle tissue of transgenic SOD1G93A mice at the mRNA and protein level. Previous studies have shown that damage of neurons physiologically causes Neuropilin1 and Semaphorin3A increase in the central nervous system and decrease in the peripheral nervous system. Our results indicate that this also occurs in ALS. Pharmacological modulation of expression and function of axon repellents could be a promising future therapeutic option in ALS. Sonja Körner, Nadine Thau‐Habermann, Ekaterini Kefalakes, Franziska Bursch, Susanne Petri https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14326?af=R European Journal of Neuroscience Expression of the axon‐guidance protein receptor Neuropilin 1 is increased in the spinal cord and decreased in muscle of a mouse model of amyotrophic lateral sclerosis

The expression of the repulsive axon‐guidance protein receptor Neuropilin 1 and its main ligand Semaphorin 3A is decreased in muscle of transgenic SOD1G93A mouse model of amyotrophic lateral sclerosis, Neuropilin 1 is further increased in the spinal cord. The major repulsive axon guidance cues therefore may be increased in CNS and decreased in PNS tissue after damage. Selective inhibition of Nrp1‐regulated pathways might be a promising novel therapeutic approach for the treatment of ALS.

 

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a degenerative motor neuron disorder. It is supposed that ALS is at least in part an axonopathy. Neuropilin 1 is an important receptor of the axon repellent Semaphorin 3A and a co‐receptor of vascular endothelial growth factor. It is probably involved in neuronal and axonal de‐/regeneration and might be of high relevance for ALS pathogenesis and/or disease progression. To elucidate whether the expression of either Neuropilin1 or Semaphorin3A is altered in ALS we investigated these proteins in human brain, spinal cord and muscle tissue of ALS‐patients and controls as well as transgenic SOD1G93A and control mice. Neuropilin1 and Semaphorin3A gene and protein expression were assessed by quantitative real‐time PCR (qRT‐PCR), western blot and immunohistochemistry. Groups were compared using either Student t‐test or Mann–Whitney U test. We observed a consistent increase of Neuropilin1 expression in the spinal cord and decrease of Neuropilin1 and Semaphorin3A in muscle tissue of transgenic SOD1G93A mice at the mRNA and protein level. Previous studies have shown that damage of neurons physiologically causes Neuropilin1 and Semaphorin3A increase in the central nervous system and decrease in the peripheral nervous system. Our results indicate that this also occurs in ALS. Pharmacological modulation of expression and function of axon repellents could be a promising future therapeutic option in ALS.

European Journal of Neuroscience, EarlyView. Expression of the axon‐guidance protein receptor Neuropilin 1 is increased in the spinal cord and decreased in muscle of a mouse model of amyotrophic lateral sclerosis doi:10.1111/ejn.14326 European Journal of Neuroscience 2019-01-16T04:39:51-08:00 European Journal of Neuroscience 10.1111/ejn.14326 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14326?af=R RESEARCH REPORT Prefrontal cortex development and emergence of self‐regulatory competence: the two cardinal features of adolescence disrupted in context of alcohol abuse Risk taking and sensation seeking, considered as idiosyncratic adolescent behaviours, concur with increased risks of alcohol misuse. In return, heavy alcohol consumption weakens prefrontal networks, disrupts cognitive performance and exacerbates impulsivity making early chronic alcohol intoxication a royal gateway to alcoholism. Abstract Adolescence is a tumultuous period in the lifetime of an individual confronted to major changes in emotional, social and cognitive appraisal. During this period of questioning and doubt, while the executive functions are still maturing, the abstract reasoning remains vague and the response inhibition loose; ultimately the adolescent scarcely resists temptation. Consequently, adolescence is often associated with uninhibited risk‐taking, reckless behaviours, among which are alcohol and illicit drugs use. Here, we discuss how the development of the prefrontal cortex (which critically contributes to rational decision‐making and temporal processing of complex events) can be associated with the idiosyncratic adolescent behaviour, and potentially uncontrolled alcohol use. Most importantly, we present clinical and preclinical evidence supporting that ethanol exposure has deleterious effects on the adolescent developing brain. Ultimately, we discuss why a late maturing prefrontal cortex represents a ripe candidate to environmental influences that contribute to shape the adolescent brain but, potentially, can also trigger lifelong maladaptive responses, including increased vulnerability to develop substance use disorder later in life. Kshitij S. Jadhav, Benjamin Boutrel https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14316?af=R European Journal of Neuroscience Prefrontal cortex development and emergence of self‐regulatory competence: the two cardinal features of adolescence disrupted in context of alcohol abuse

Risk taking and sensation seeking, considered as idiosyncratic adolescent behaviours, concur with increased risks of alcohol misuse. In return, heavy alcohol consumption weakens prefrontal networks, disrupts cognitive performance and exacerbates impulsivity making early chronic alcohol intoxication a royal gateway to alcoholism.

 

Abstract

Adolescence is a tumultuous period in the lifetime of an individual confronted to major changes in emotional, social and cognitive appraisal. During this period of questioning and doubt, while the executive functions are still maturing, the abstract reasoning remains vague and the response inhibition loose; ultimately the adolescent scarcely resists temptation. Consequently, adolescence is often associated with uninhibited risk‐taking, reckless behaviours, among which are alcohol and illicit drugs use. Here, we discuss how the development of the prefrontal cortex (which critically contributes to rational decision‐making and temporal processing of complex events) can be associated with the idiosyncratic adolescent behaviour, and potentially uncontrolled alcohol use. Most importantly, we present clinical and preclinical evidence supporting that ethanol exposure has deleterious effects on the adolescent developing brain. Ultimately, we discuss why a late maturing prefrontal cortex represents a ripe candidate to environmental influences that contribute to shape the adolescent brain but, potentially, can also trigger lifelong maladaptive responses, including increased vulnerability to develop substance use disorder later in life.

European Journal of Neuroscience, EarlyView. Prefrontal cortex development and emergence of self‐regulatory competence: the two cardinal features of adolescence disrupted in context of alcohol abuse doi:10.1111/ejn.14316 European Journal of Neuroscience 2019-01-16T04:35:25-08:00 European Journal of Neuroscience 10.1111/ejn.14316 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14316?af=R Special Issue Review Convergent synaptic inputs to layer 1 cells of mouse cortex Layer 1 neurons received convergent glutamatergic and GABAergic inputs from layer 2/3 and lower cortical laminae, GABAergic inputs from nearby layer 1 cells, long‐range cortical projections, and subcortical inputs from matrix thalamus and neuromodulator systems. Abstract We used whole cell recordings from slice preparations of mouse cortex to identify various inputs to neurons of layer 1. Two sensory cortical areas were targeted: a primary somatosensory area, namely, the barrel cortex of S1, and a higher order visual area, namely, V2M. Results were similar from both areas. By activating local inputs using photostimulation with caged glutamate, we also identified glutamatergic (and possibly GABAergic) inputs from all lower layers plus GABAergic inputs from nearby layer 1 neurons. However, the patterns of such inputs to layer 1 neurons showed great variation among cells. In separate experiments, we found that electrical stimulation of axons running parallel to the cortical surface in layer 1 also evoked a variety of convergent input types to layer 1 neurons, including glutamatergic “drivers” and “modulators” plus classic modulatory inputs, including serotonergic, nicotinic, α‐ and β‐adrenergic, from subcortical sites. Given that these layer 1 cells significantly affect the responses of other cortical neurons, especially via affecting the apical dendrites of pyramidal cells so important to cortical functioning, their role in cortical processing is significant. We believe that the data presented here lead to better understanding of the functioning of layer 1 neurons in their role of influencing cortical processing. Ying‐Wan Lam, S. Murray Sherman https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14324?af=R European Journal of Neuroscience Convergent synaptic inputs to layer 1 cells of mouse cortex

Layer 1 neurons received convergent glutamatergic and GABAergic inputs from layer 2/3 and lower cortical laminae, GABAergic inputs from nearby layer 1 cells, long‐range cortical projections, and subcortical inputs from matrix thalamus and neuromodulator systems.

 

Abstract

We used whole cell recordings from slice preparations of mouse cortex to identify various inputs to neurons of layer 1. Two sensory cortical areas were targeted: a primary somatosensory area, namely, the barrel cortex of S1, and a higher order visual area, namely, V2M. Results were similar from both areas. By activating local inputs using photostimulation with caged glutamate, we also identified glutamatergic (and possibly GABAergic) inputs from all lower layers plus GABAergic inputs from nearby layer 1 neurons. However, the patterns of such inputs to layer 1 neurons showed great variation among cells. In separate experiments, we found that electrical stimulation of axons running parallel to the cortical surface in layer 1 also evoked a variety of convergent input types to layer 1 neurons, including glutamatergic “drivers” and “modulators” plus classic modulatory inputs, including serotonergic, nicotinic, α‐ and β‐adrenergic, from subcortical sites. Given that these layer 1 cells significantly affect the responses of other cortical neurons, especially via affecting the apical dendrites of pyramidal cells so important to cortical functioning, their role in cortical processing is significant. We believe that the data presented here lead to better understanding of the functioning of layer 1 neurons in their role of influencing cortical processing.

European Journal of Neuroscience, EarlyView. Convergent synaptic inputs to layer 1 cells of mouse cortex doi:10.1111/ejn.14324 European Journal of Neuroscience 2019-01-16T04:32:10-08:00 European Journal of Neuroscience 10.1111/ejn.14324 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14324?af=R RESEARCH REPORT Science in flux: Registered reports and beyond at the European Journal of Neuroscience Christopher D. Chambers, Birte Forstmann, J. Andrew Pruszynski https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14319?af=R European Journal of Neuroscience, EarlyView. Science in flux: Registered reports and beyond at the European Journal of Neuroscience doi:10.1111/ejn.14319 European Journal of Neuroscience 2019-01-16T04:23:37-08:00 European Journal of Neuroscience 10.1111/ejn.14319 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14319?af=R EDITORIAL Spatial impact of microglial distribution on dynamics of dendritic spines Simultaneous imaging of dendritic spines and microglia in vivo revealed that a distance between microglial cell body and spine is a critical parameter in spine stability. Large‐volume optical reconstruction with a tissue‐clearing technique visualized a mutually exclusive distribution of microglia across cortical layers. Our results suggest that the spatial arrangement of microglia generates repetitive domains of instability of spines along dendrites. Abstract Microglia regulate synapse stability and remodeling through multiple molecular pathways. Regulated spatial distribution of microglia within nervous tissues may affect synapse dynamics. Here, we focused on the spatial relationship between microglia and spine synapses in the mouse neocortex and found that the distance between microglial cell bodies (MCBs) and spines is a critical parameter in spine stability. The region close to MCBs contains microglial processes with higher density and with more spine contacts. This region also shows more extensive exploration of tissue space by microglial processes. To test if the relative positions between MCBs and spines are important for spine stability, we simultaneously imaged spines and microglia in vivo and found negative correlation between spine–MCB distance and spine stability. Optical clearing methods enabled us to record the positions of all microglia in a large cortical volume and indicated their mutually exclusive distribution with similar density across cortical layers. This spatial arrangement of microglia is responsible for the repeated appearance of domains close to MCBs along dendritic arborization. The microglial position was largely independent of other cellular components. These results suggest that the spatial arrangement of microglia is critical for generating repetitive domains of synaptic instability along dendrites, which operates independently of other glial components. Tadatsune Iida, Shinji Tanaka, Shigeo Okabe https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14325?af=R European Journal of Neuroscience Spatial impact of microglial distribution on dynamics of dendritic spines

Simultaneous imaging of dendritic spines and microglia in vivo revealed that a distance between microglial cell body and spine is a critical parameter in spine stability. Large‐volume optical reconstruction with a tissue‐clearing technique visualized a mutually exclusive distribution of microglia across cortical layers. Our results suggest that the spatial arrangement of microglia generates repetitive domains of instability of spines along dendrites.

 

Abstract

Microglia regulate synapse stability and remodeling through multiple molecular pathways. Regulated spatial distribution of microglia within nervous tissues may affect synapse dynamics. Here, we focused on the spatial relationship between microglia and spine synapses in the mouse neocortex and found that the distance between microglial cell bodies (MCBs) and spines is a critical parameter in spine stability. The region close to MCBs contains microglial processes with higher density and with more spine contacts. This region also shows more extensive exploration of tissue space by microglial processes. To test if the relative positions between MCBs and spines are important for spine stability, we simultaneously imaged spines and microglia in vivo and found negative correlation between spine–MCB distance and spine stability. Optical clearing methods enabled us to record the positions of all microglia in a large cortical volume and indicated their mutually exclusive distribution with similar density across cortical layers. This spatial arrangement of microglia is responsible for the repeated appearance of domains close to MCBs along dendritic arborization. The microglial position was largely independent of other cellular components. These results suggest that the spatial arrangement of microglia is critical for generating repetitive domains of synaptic instability along dendrites, which operates independently of other glial components.

European Journal of Neuroscience, EarlyView. Spatial impact of microglial distribution on dynamics of dendritic spinesdoi:10.1111/ejn.14325European Journal of Neuroscience2019-01-16T12:00:00-08:00European Journal of Neuroscience10.1111/ejn.14325 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14325?af=RRESEARCH REPORTVolume of motor area predicts motor impulsivity Abstract Impulsivity is a personality trait associated with many maladaptive behaviors. Trait impulsivity is typically divided into three different dimensions, including attentional impulsiveness, motor impulsiveness, and non‐planning impulsiveness. The present work aimed to investigate the neuroanatomical basis of the multidimensional impulsivity trait. Eighty‐four healthy subjects were studied with structural magnetic resonance imaging. Multiple regression analyses revealed that the score of motor impulsiveness was negatively correlated with gray matter volumes of the right supplementary motor area and paracentral lobule. A machine‐learning based prediction analysis indicated that decreased gray matter volumes of the supplementary motor area and paracentral lobule strongly predicted deficits in motor impulsiveness control. Our findings provide insights into the predictive role of motor brain structures in motor impulsivity and inhibition control. This article is protected by copyright. All rights reserved. Hui Ai, Yuanyuan Xin, Yuejia Luo, Ruolei Gu, Pengfei Xu https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14339?af=R

Abstract

Impulsivity is a personality trait associated with many maladaptive behaviors. Trait impulsivity is typically divided into three different dimensions, including attentional impulsiveness, motor impulsiveness, and non‐planning impulsiveness. The present work aimed to investigate the neuroanatomical basis of the multidimensional impulsivity trait. Eighty‐four healthy subjects were studied with structural magnetic resonance imaging. Multiple regression analyses revealed that the score of motor impulsiveness was negatively correlated with gray matter volumes of the right supplementary motor area and paracentral lobule. A machine‐learning based prediction analysis indicated that decreased gray matter volumes of the supplementary motor area and paracentral lobule strongly predicted deficits in motor impulsiveness control. Our findings provide insights into the predictive role of motor brain structures in motor impulsivity and inhibition control.

This article is protected by copyright. All rights reserved.

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. Volume of motor area predicts motor impulsivity doi:10.1111/ejn.14339 European Journal of Neuroscience 2019-01-12T05:49:56-08:00 European Journal of Neuroscience 10.1111/ejn.14339 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14339?af=R Short Communication Stronger responses to darks along the ventral pathway of the cat visual cortex Psychophysical and neurophysiological data suggest that neurons respond preferentially to light decrements across the cortical hierarchy. Here, we addressed this issue by assessing the neuronal responses to brights and darks in a cortical area along the ventral stream in cats (area 21a). Our results show that neurons exhibit stronger responses to darks with receptive fields exhibiting larger dark subfields. Our findings provide new insights into the ventral stream's processing of luminance. Abstract Light increments (brights) and decrements (darks) are differently processed throughout the early visual system. It is well known that a bias towards faster and stronger responses to darks is present in the retina, lateral geniculate nucleus and primary visual cortex. In humans, psychophysical and neurophysiological data indicate that darks are better detected than brights, suggesting that the dark bias found in early visual areas is transmitted across the cortical hierarchy. Here, we tested this assumption by investigating the spatiotemporal features of responses to brights and darks in area 21a, a gateway area of the cat ventral stream, using reverse correlation analysis of a sparse noise stimulus. The receptive field of most 21a neurons exhibited larger dark subfields. Additionally, the amplitude of the responses to darks was considerably greater than those evoked by brights. In the temporal domain, no differences were found between the response peak latency. Thus, the present study supports the notion that bright/dark asymmetries are transmitted throughout the cortical hierarchy and further, that the luminance processing varies as a function of the position in the cortical hierarchy, dark preference being strongly enhanced (in the spatial domain and response amplitude) along the ventral pathway. Oliveira Ferreira de Souza Bruno, Casanova Christian https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14297?af=R European Journal of Neuroscience Stronger responses to darks along the ventral pathway of the cat visual cortex

Psychophysical and neurophysiological data suggest that neurons respond preferentially to light decrements across the cortical hierarchy. Here, we addressed this issue by assessing the neuronal responses to brights and darks in a cortical area along the ventral stream in cats (area 21a). Our results show that neurons exhibit stronger responses to darks with receptive fields exhibiting larger dark subfields. Our findings provide new insights into the ventral stream's processing of luminance.

 

Abstract

Light increments (brights) and decrements (darks) are differently processed throughout the early visual system. It is well known that a bias towards faster and stronger responses to darks is present in the retina, lateral geniculate nucleus and primary visual cortex. In humans, psychophysical and neurophysiological data indicate that darks are better detected than brights, suggesting that the dark bias found in early visual areas is transmitted across the cortical hierarchy. Here, we tested this assumption by investigating the spatiotemporal features of responses to brights and darks in area 21a, a gateway area of the cat ventral stream, using reverse correlation analysis of a sparse noise stimulus. The receptive field of most 21a neurons exhibited larger dark subfields. Additionally, the amplitude of the responses to darks was considerably greater than those evoked by brights. In the temporal domain, no differences were found between the response peak latency. Thus, the present study supports the notion that bright/dark asymmetries are transmitted throughout the cortical hierarchy and further, that the luminance processing varies as a function of the position in the cortical hierarchy, dark preference being strongly enhanced (in the spatial domain and response amplitude) along the ventral pathway.

European Journal of Neuroscience, EarlyView. Stronger responses to darks along the ventral pathway of the cat visual cortex doi:10.1111/ejn.14297 European Journal of Neuroscience 2019-01-11T10:30:28-08:00 European Journal of Neuroscience 10.1111/ejn.14297 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14297?af=R RESEARCH REPORT Bi‐directional modulation of food habit expression by the endocannabinoid system Mice were trained to habitually respond for food. Administration of the putative endocannabinoid transporter inhibitor, AM404, decreased habitual responding. This effect of AM404 was abrogated by pre‐treatment with JZL184, a catabolic enzyme inhibitor that increases synaptic levels of the endocannabinoid 2‐arachidonoyl glycerol. We propose that the mechanism by which AM404 reduces habitual responding is through the prevention of endocannabinoid release. Abstract The compulsive, habitual behaviors that have been observed in individuals diagnosed with substance use disorders may be due to disruptions in the neural circuits that mediate goal‐directed actions. The endocannabinoid system has been shown to play a critical role in habit learning, but the role of this neuromodulatory system in habit expression is unclear. Here, we investigated the role of the endocannabinoid system in established habitual actions using contingency degradation in male C57BL/6 mice. We found that administration of the endocannabinoid transport inhibitor AM404 reduced habitual responding for food and that antagonism of cannabinoid receptor type 1 (CB1), but not transient receptor potential cation subfamily V (TRPV1), receptors produced a similar reduction in habitual responding. Moreover, pharmacological stimulation of CB1 receptors increased habitual responding for food. Co‐administration of an enzyme inhibitor that selectively increases the endocannabinoid 2‐arachidonoyl glycerol (2‐AG) with AM404 partially restored habitual responding for food. Together, these findings demonstrate an important role for the endocannabinoid system in the expression of habits and provide novel insights into potential pharmacological strategies for reducing habitual behaviors in mental disorders. Carol A. Gianessi, Stephanie M. Groman, Jane R. Taylor https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14330?af=R European Journal of Neuroscience Bi‐directional modulation of food habit expression by the endocannabinoid system

Mice were trained to habitually respond for food. Administration of the putative endocannabinoid transporter inhibitor, AM404, decreased habitual responding. This effect of AM404 was abrogated by pre‐treatment with JZL184, a catabolic enzyme inhibitor that increases synaptic levels of the endocannabinoid 2‐arachidonoyl glycerol. We propose that the mechanism by which AM404 reduces habitual responding is through the prevention of endocannabinoid release.

 

Abstract

The compulsive, habitual behaviors that have been observed in individuals diagnosed with substance use disorders may be due to disruptions in the neural circuits that mediate goal‐directed actions. The endocannabinoid system has been shown to play a critical role in habit learning, but the role of this neuromodulatory system in habit expression is unclear. Here, we investigated the role of the endocannabinoid system in established habitual actions using contingency degradation in male C57BL/6 mice. We found that administration of the endocannabinoid transport inhibitor AM404 reduced habitual responding for food and that antagonism of cannabinoid receptor type 1 (CB1), but not transient receptor potential cation subfamily V (TRPV1), receptors produced a similar reduction in habitual responding. Moreover, pharmacological stimulation of CB1 receptors increased habitual responding for food. Co‐administration of an enzyme inhibitor that selectively increases the endocannabinoid 2‐arachidonoyl glycerol (2‐AG) with AM404 partially restored habitual responding for food. Together, these findings demonstrate an important role for the endocannabinoid system in the expression of habits and provide novel insights into potential pharmacological strategies for reducing habitual behaviors in mental disorders.

European Journal of Neuroscience, EarlyView. Bi‐directional modulation of food habit expression by the endocannabinoid systemdoi:10.1111/ejn.14330European Journal of Neuroscience2019-01-11T10:23:55-08:00European Journal of Neuroscience10.1111/ejn.14330 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14330?af=RRESEARCH REPORT Circadian Regulation of Membrane Physiology in Neural Oscillators Throughout the Brain Abstract Twenty‐four‐hour rhythmicity in physiology and behavior are driven by changes in neurophysiological activity that vary across the light‐dark and rest‐activity cycle. Although this neural code is most prominent in neurons of the primary circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus, there are many other regions in the brain where region‐specific function and behavioral rhythmicity may be encoded by changes in electrical properties of those neurons. In this review, we explore the existing evidence for molecular clocks and/or neurophysiological rhythms (i.e., 24‐h) in brain regions outside the SCN. In addition, we highlight the brain regions that are ripe for future investigation into the critical role of circadian rhythmicity for local oscillators. For example, the cerebellum expresses rhythmicity in over 2,000 gene transcripts, and yet we know very little about how circadian regulation drives 24‐h changes in the neural coding responsible for motor coordination. Finally, we conclude with a discussion of how our understanding of circadian regulation of electrical properties may yield insight into disease mechanisms which may lead to novel chronotherapeutic strategies in the future. This article is protected by copyright. All rights reserved. Jodi R. Paul, Jennifer A. Davis, Lacy K. Goode, Bryan K. Becker, Allison Fusilier, Aidan Meador‐Woodruff, Karen L. Gamble https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14343?af=R

Abstract

Twenty‐four‐hour rhythmicity in physiology and behavior are driven by changes in neurophysiological activity that vary across the light‐dark and rest‐activity cycle. Although this neural code is most prominent in neurons of the primary circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus, there are many other regions in the brain where region‐specific function and behavioral rhythmicity may be encoded by changes in electrical properties of those neurons. In this review, we explore the existing evidence for molecular clocks and/or neurophysiological rhythms (i.e., 24‐h) in brain regions outside the SCN. In addition, we highlight the brain regions that are ripe for future investigation into the critical role of circadian rhythmicity for local oscillators. For example, the cerebellum expresses rhythmicity in over 2,000 gene transcripts, and yet we know very little about how circadian regulation drives 24‐h changes in the neural coding responsible for motor coordination. Finally, we conclude with a discussion of how our understanding of circadian regulation of electrical properties may yield insight into disease mechanisms which may lead to novel chronotherapeutic strategies in the future.

This article is protected by copyright. All rights reserved.

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. Circadian Regulation of Membrane Physiology in Neural Oscillators Throughout the Braindoi:10.1111/ejn.14343European Journal of Neuroscience2019-01-11T10:32:58-08:00European Journal of Neuroscience10.1111/ejn.14343 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14343?af=RSpecial Issue Review Separate cortical and hippocampal cell populations target the rat nucleus reuniens and mammillary bodies Abstract Nucleus reuniens receives dense projections from both the hippocampus and the frontal cortices. Reflecting these connections, this nucleus is thought to enable executive functions, including those involving spatial learning. The mammillary bodies, which also support spatial learning, again receive dense hippocampal inputs, as well as lighter projections from medial frontal areas. The present study, therefore, compared the sources of these inputs to nucleus reuniens and the mammillary bodies. Retrograde tracer injections in rats showed how these two diencephalic sites receive projections from separate cell populations, often from adjacent layers in the same cortical areas. In the subiculum, which projects strongly to both sites, the mammillary body inputs originate from a homogenous pyramidal cell population in more superficial levels, while the cells that target nucleus reuniens most often originate from cells positioned at a deeper level. In these deeper levels, a more morphologically diverse set of subiculum cells contributes to the thalamic projection, especially at septal levels. While both diencephalic sites also receive medial frontal inputs, those to nucleus reuniens are especially dense. The densest inputs to the mammillary bodies appear to arise from the dorsal peduncular cortex, where the cells are mostly separate from deeper neurons that project to nucleus reuniens. Again, in those other cortical regions that innervate both nucleus reuniens and the mammillary bodies, there was no evidence of collateral projections. The findings support the notion that these diencephalic nuclei represent components of distinct, but complementary, systems that support different aspects of cognition. This article is protected by copyright. All rights reserved. Mathias L. Mathiasen, Eman Amin, Andrew J. D. Nelson, Christopher M. Dillingham, Shane M. O'Mara, John P. Aggleton https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14341?af=R

Abstract

Nucleus reuniens receives dense projections from both the hippocampus and the frontal cortices. Reflecting these connections, this nucleus is thought to enable executive functions, including those involving spatial learning. The mammillary bodies, which also support spatial learning, again receive dense hippocampal inputs, as well as lighter projections from medial frontal areas. The present study, therefore, compared the sources of these inputs to nucleus reuniens and the mammillary bodies. Retrograde tracer injections in rats showed how these two diencephalic sites receive projections from separate cell populations, often from adjacent layers in the same cortical areas. In the subiculum, which projects strongly to both sites, the mammillary body inputs originate from a homogenous pyramidal cell population in more superficial levels, while the cells that target nucleus reuniens most often originate from cells positioned at a deeper level. In these deeper levels, a more morphologically diverse set of subiculum cells contributes to the thalamic projection, especially at septal levels. While both diencephalic sites also receive medial frontal inputs, those to nucleus reuniens are especially dense. The densest inputs to the mammillary bodies appear to arise from the dorsal peduncular cortex, where the cells are mostly separate from deeper neurons that project to nucleus reuniens. Again, in those other cortical regions that innervate both nucleus reuniens and the mammillary bodies, there was no evidence of collateral projections. The findings support the notion that these diencephalic nuclei represent components of distinct, but complementary, systems that support different aspects of cognition.

This article is protected by copyright. All rights reserved.

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. Separate cortical and hippocampal cell populations target the rat nucleus reuniens and mammillary bodiesdoi:10.1111/ejn.14341European Journal of Neuroscience2019-01-11T10:08:10-08:00European Journal of Neuroscience10.1111/ejn.14341 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14341?af=RResearch Report Synchronized activation of striatal direct and indirect pathways underlies the behavior in unilateral dopamine‐depleted mice Abstract For more than 3 decades it has been known, that striatal neurons become hyperactive after the loss of dopamine input, but the involvement of dopamine (DA) D1‐ or D2‐receptor‐expressing neurons has only been demonstrated indirectly. By recording neuronal activity using fluorescent calcium indicators in D1 or D2 eGFP‐expressing mice, we showed that following dopamine depletion, both types of striatal output neurons are involved in the large increase in neuronal activity generating a characteristic cell assembly of particular neurons that dominate the pattern. When we expressed channelrhodopsin in all the output neurons, light activation in freely moving animals, caused turning like that following dopamine loss. However, if the light stimulation was patterned in pulses the animals circled in the other direction. To explore the neuronal participation during this stimulation we infected normal mice with channelrhodopsin and calcium indicator in striatal output neurons. In slices made from these animals, continuous light stimulation for 15 s induced many cells to be active together and a particular dominant group of neurons, while light in patterned pulses activated fewer cells in more variable groups. These results suggest that the simultaneous activity of a large dominant group of striatal output neurons is intimately associated with parkinsonian symptoms. This article is protected by copyright. All rights reserved. Omar Jáidar, Luis Carrillo‐Reid, Yoko Nakano, Violeta Gisselle Lopez‐Huerta, Arturo Hernandez‐Cruz, José Bargas, Marianela Garcia‐Munoz, Gordon William Arbuthnott https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14344?af=R

Abstract

For more than 3 decades it has been known, that striatal neurons become hyperactive after the loss of dopamine input, but the involvement of dopamine (DA) D1‐ or D2‐receptor‐expressing neurons has only been demonstrated indirectly. By recording neuronal activity using fluorescent calcium indicators in D1 or D2 eGFP‐expressing mice, we showed that following dopamine depletion, both types of striatal output neurons are involved in the large increase in neuronal activity generating a characteristic cell assembly of particular neurons that dominate the pattern. When we expressed channelrhodopsin in all the output neurons, light activation in freely moving animals, caused turning like that following dopamine loss. However, if the light stimulation was patterned in pulses the animals circled in the other direction. To explore the neuronal participation during this stimulation we infected normal mice with channelrhodopsin and calcium indicator in striatal output neurons. In slices made from these animals, continuous light stimulation for 15 s induced many cells to be active together and a particular dominant group of neurons, while light in patterned pulses activated fewer cells in more variable groups. These results suggest that the simultaneous activity of a large dominant group of striatal output neurons is intimately associated with parkinsonian symptoms.

This article is protected by copyright. All rights reserved.

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. Synchronized activation of striatal direct and indirect pathways underlies the behavior in unilateral dopamine‐depleted micedoi:10.1111/ejn.14344European Journal of Neuroscience2019-01-11T09:20:51-08:00European Journal of Neuroscience10.1111/ejn.14344 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14344?af=RResearch Report “Higher education” ‐ Substance use among Berlin college students Abstract Berlin is internationally known for its intense nightlife associated with high rates of psychoactive substance use. Previous studies conducted in other cities indicated college students as a group at high risk for substance (mis‐)use, that was associated with individual psychological and cognitive impairments as well as lower academic performance. The aim of this study was to provide detailed data about the substance use patterns of Berlin college students. In addition, major protective factors and risk factors were analysed. An online questionnaire assessing sociodemographic data and various relevant aspects of both legal and illegal substance use such as consumption pattern and frequency as well as risk‐taking behaviour was developed and distributed among colleges in Berlin. A sample of 9,351 participants from 17 different colleges in Berlin completed the questionnaire. The study revealed high lifetime (69.3%), past year (45.9%) and past month (28.3%) prevalence of illicit substance use in the sample. Daily tobacco‐smoking, a mental disorder diagnosis, a positive screening for problematic consumption (Cage‐AID), bisexual orientation and living in open‐relationship were main factors positively associated with the prevalence and the extent of illicit substance use. Students in Berlin appear to show higher rates of illicit substance use than was previously reported for age‐matched individuals in the general German population and college‐students in other cities. Thus, they are a relevant target group for early prevention and intervention concerning substance use and abuse. This article is protected by copyright. All rights reserved. Leonard Viohl, Felicitas Ernst, Julian Gabrysch, Moritz B. Petzold, Stephan Köhler, Andreas Ströhle, Felix Betzler https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14340?af=R

Abstract

Berlin is internationally known for its intense nightlife associated with high rates of psychoactive substance use. Previous studies conducted in other cities indicated college students as a group at high risk for substance (mis‐)use, that was associated with individual psychological and cognitive impairments as well as lower academic performance.

The aim of this study was to provide detailed data about the substance use patterns of Berlin college students. In addition, major protective factors and risk factors were analysed.

An online questionnaire assessing sociodemographic data and various relevant aspects of both legal and illegal substance use such as consumption pattern and frequency as well as risk‐taking behaviour was developed and distributed among colleges in Berlin.

A sample of 9,351 participants from 17 different colleges in Berlin completed the questionnaire. The study revealed high lifetime (69.3%), past year (45.9%) and past month (28.3%) prevalence of illicit substance use in the sample. Daily tobacco‐smoking, a mental disorder diagnosis, a positive screening for problematic consumption (Cage‐AID), bisexual orientation and living in open‐relationship were main factors positively associated with the prevalence and the extent of illicit substance use.

Students in Berlin appear to show higher rates of illicit substance use than was previously reported for age‐matched individuals in the general German population and college‐students in other cities. Thus, they are a relevant target group for early prevention and intervention concerning substance use and abuse.

This article is protected by copyright. All rights reserved.

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. “Higher education” ‐ Substance use among Berlin college studentsdoi:10.1111/ejn.14340European Journal of Neuroscience2019-01-11T09:03:41-08:00European Journal of Neuroscience10.1111/ejn.14340 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14340?af=RSpecial Issue Article The role of aquaporin‐4 and transient receptor potential vaniloid isoform 4 channels in the development of cytotoxic edema and associated extracellular diffusion parameter changes Abstract The proper function of the nervous system is dependent on the balance of ions and water between the intracellular and extracellular space (ECS). It has been suggested that the interaction of aquaporin‐4 (AQP4) and the transient receptor potential vaniloid isoform 4 (TRPV4) channels play a role in water balance and cell volumeregulation, and indirectly, of the ECS volume. Using the real time‐iontophoretic method, we studied the changes of the ECS diffusion parameters: ECS volume fraction α (α = ECS volume fraction/total tissue volume) and tortuosity λ (λ2 = free/apparent diffusion coefficient) in mice with a genetic deficiency of AQP4 or TRPV4 channels, and in control animals. The cytotoxix edema models that were used included: mild and severe hypotonic stress or oxygen glucose deprivation (OGD) in situ and terminal ischemia/anoxia in vivo. This study shows that an AQP4 or TRPV4 deficit slows down the ECS volume shrinkage during severe ischemia in vivo. We further demonstrate that a TRPV4 deficit slows down the velocity and attenuates an extent of the ECS volume decrease during OGD treatment in situ. However, in any of the cytotoxic edema models in situ (OGD, mild or severe hypotonic stress), we did not detect any alterations in the cell swelling or volume regulation caused by AQP4 deficiency. Overall, our results indicate that the AQP4 and TRPV4 channels may play a crucial role in severe pathological states associated with their overexpression and enhanced cell swelling. However, detailed interplay between AQP4 and TRPV4 channels requires further studies and additional research. This article is protected by copyright. All rights reserved. Martina Chmelova, Petra Sucha, Marcel Bochin, Ivan Vorisek, Helena Pivonkova, Zuzana Hermanova, Miroslava Anderova, Lydia Vargova https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14338?af=R

Abstract

The proper function of the nervous system is dependent on the balance of ions and water between the intracellular and extracellular space (ECS). It has been suggested that the interaction of aquaporin‐4 (AQP4) and the transient receptor potential vaniloid isoform 4 (TRPV4) channels play a role in water balance and cell volumeregulation, and indirectly, of the ECS volume. Using the real time‐iontophoretic method, we studied the changes of the ECS diffusion parameters: ECS volume fraction α (α = ECS volume fraction/total tissue volume) and tortuosity λ (λ2 = free/apparent diffusion coefficient) in mice with a genetic deficiency of AQP4 or TRPV4 channels, and in control animals. The cytotoxix edema models that were used included: mild and severe hypotonic stress or oxygen glucose deprivation (OGD) in situ and terminal ischemia/anoxia in vivo. This study shows that an AQP4 or TRPV4 deficit slows down the ECS volume shrinkage during severe ischemia in vivo. We further demonstrate that a TRPV4 deficit slows down the velocity and attenuates an extent of the ECS volume decrease during OGD treatment in situ. However, in any of the cytotoxic edema models in situ (OGD, mild or severe hypotonic stress), we did not detect any alterations in the cell swelling or volume regulation caused by AQP4 deficiency. Overall, our results indicate that the AQP4 and TRPV4 channels may play a crucial role in severe pathological states associated with their overexpression and enhanced cell swelling. However, detailed interplay between AQP4 and TRPV4 channels requires further studies and additional research.

This article is protected by copyright. All rights reserved.

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. The role of aquaporin‐4 and transient receptor potential vaniloid isoform 4 channels in the development of cytotoxic edema and associated extracellular diffusion parameter changesdoi:10.1111/ejn.14338European Journal of Neuroscience2019-01-11T08:05:53-08:00European Journal of Neuroscience10.1111/ejn.14338 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14338?af=RResearch Report Epigenetic regulation of myelination in health and disease Abstract Myelin is lipid‐rich structure that is necessary to avoid leakage of electric signals and to ensure saltatory impulse conduction along axons. Oligodendrocytes in central nervous system (CNS) and Schwann cells in peripheral nervous system (PNS) are responsible for myelin formation. Axonal demyelination after injury or diseases greatly impairs normal nervous system function. Therefore, understanding how the myelination process is programmed, coordinated, and maintained is crucial for developing therapeutic strategies for remyelination in the nervous system. Epigenetic mechanisms have been recognized as a fundamental contributor in this process. In recent years, histone modification, DNA modification, ATP‐dependent chromatin remodeling, and non‐coding RNA modulation are very active area of investigation. We will present a conceptual framework that integrates crucial epigenetic mechanisms with the regulation of oligodendrocyte and Schwann cell lineage progression during development and myelin degeneration in pathological conditions. It is anticipated that a refined understanding of the molecular basis of myelination will aid in the development of treatment strategies for debilitating disorders that involve demyelination, such as multiple sclerosis in the CNS and neuropathies in the PNS. This article is protected by copyright. All rights reserved. Guozhen Lu, Ming Zhang, Jian Wang, Kaixiang Zhang, Shengxi Wu, Xianghui Zhao https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14337?af=R

Abstract

Myelin is lipid‐rich structure that is necessary to avoid leakage of electric signals and to ensure saltatory impulse conduction along axons. Oligodendrocytes in central nervous system (CNS) and Schwann cells in peripheral nervous system (PNS) are responsible for myelin formation. Axonal demyelination after injury or diseases greatly impairs normal nervous system function. Therefore, understanding how the myelination process is programmed, coordinated, and maintained is crucial for developing therapeutic strategies for remyelination in the nervous system. Epigenetic mechanisms have been recognized as a fundamental contributor in this process. In recent years, histone modification, DNA modification, ATP‐dependent chromatin remodeling, and non‐coding RNA modulation are very active area of investigation. We will present a conceptual framework that integrates crucial epigenetic mechanisms with the regulation of oligodendrocyte and Schwann cell lineage progression during development and myelin degeneration in pathological conditions. It is anticipated that a refined understanding of the molecular basis of myelination will aid in the development of treatment strategies for debilitating disorders that involve demyelination, such as multiple sclerosis in the CNS and neuropathies in the PNS.

This article is protected by copyright. All rights reserved.

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. Epigenetic regulation of myelination in health and diseasedoi:10.1111/ejn.14337European Journal of Neuroscience2019-01-11T08:03:13-08:00European Journal of Neuroscience10.1111/ejn.14337 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14337?af=RReview Article Encoding of kinetic and kinematic movement parameters in the sensorimotor cortex: A Brain‐Computer Interface perspective Abstract For severely paralyzed people, Brain‐Computer Interfaces (BCIs) can potentially replace lost motor output and provide a brain‐based control signal for augmentative and alternative communication devices or neuroprosthetics. Many BCIs focus on neuronal signals acquired from the hand area of the sensorimotor cortex, employing changes in the patterns of neuronal firing or spectral power associated with one or more types of hand movement. Hand and finger movement can be described by two groups of movement features, namely kinematics (spatial and motion aspects) and kinetics (muscles and forces). Despite extensive primate and human research, it is not fully understood how these features are represented in the SMC and how they lead to the appropriate movement. Yet, the available information may provide insight into which features are most suitable for BCI control. To that purpose, the current paper provides an in‐depth review on the movement features encoded in the SMC. Even though there is no consensus on how exactly the SMC generates movement, we conclude that some parameters are well represented in the SMC and can be accurately used for BCI control with discrete as well as continuous feedback. However, the vast evidence also suggests that movement should be interpreted as a combination of multiple parameters rather than isolated ones, pleading for further exploration of sensorimotor control models for accurate BCI control. This article is protected by copyright. All rights reserved. Mariana P. Branco, Lisanne M. de Boer, Nick F. Ramsey, Mariska J. Vansteensel https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14342?af=R

Abstract

For severely paralyzed people, Brain‐Computer Interfaces (BCIs) can potentially replace lost motor output and provide a brain‐based control signal for augmentative and alternative communication devices or neuroprosthetics. Many BCIs focus on neuronal signals acquired from the hand area of the sensorimotor cortex, employing changes in the patterns of neuronal firing or spectral power associated with one or more types of hand movement. Hand and finger movement can be described by two groups of movement features, namely kinematics (spatial and motion aspects) and kinetics (muscles and forces). Despite extensive primate and human research, it is not fully understood how these features are represented in the SMC and how they lead to the appropriate movement. Yet, the available information may provide insight into which features are most suitable for BCI control. To that purpose, the current paper provides an in‐depth review on the movement features encoded in the SMC. Even though there is no consensus on how exactly the SMC generates movement, we conclude that some parameters are well represented in the SMC and can be accurately used for BCI control with discrete as well as continuous feedback. However, the vast evidence also suggests that movement should be interpreted as a combination of multiple parameters rather than isolated ones, pleading for further exploration of sensorimotor control models for accurate BCI control.

This article is protected by copyright. All rights reserved.

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. Encoding of kinetic and kinematic movement parameters in the sensorimotor cortex: A Brain‐Computer Interface perspective doi:10.1111/ejn.14342 European Journal of Neuroscience 2019-01-11T12:00:00-08:00 European Journal of Neuroscience 10.1111/ejn.14342 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14342?af=R Review Article Believing is representation mediated by the dopamine brain system Rüdiger J. Seitz, Raymond F. Paloutzian, Hans‐Ferdinand Angel https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14317?af=R European Journal of Neuroscience, EarlyView. Believing is representation mediated by the dopamine brain system doi:10.1111/ejn.14317 European Journal of Neuroscience 2019-01-09T04:44:23-08:00 European Journal of Neuroscience 10.1111/ejn.14317 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14317?af=R FEATURED PAPER COMMENTARY Polymorphisms in dopaminergic genes predict proactive processes of response inhibition Here, we report that a genetic risk score (uGRS) combining rs686/A and rs1800497/T influences post‐error slowing (PES), a measure of proactive response inhibition, in a Go/No‐Go task. Even in our young sample (N = 265; age: M = 24.6, range = 18–40), age mediates the relationship between uGRS and PES; a higher uGRS seems to allow older subjects to engage proactive inhibition significantly more than young subjects to compensate for age‐related decay in the ability to withhold a prepotent response. Abstract The ability to inhibit a prepared emotional or motor action is difficult but critical to everyday functioning. It is well‐established that response inhibition relies on the dopaminergic system in the basal ganglia. However, response inhibition is often measured imprecisely due to a process which slows our responses and increases subsequent inhibition success known as proactive inhibition. As the role of the dopamine system in proactive inhibition is unclear, we investigated the contribution of dopaminergic genes to proactive inhibition. We operationalised proactive inhibition as slower responses after failures to inhibit a response in a Go/No‐Go paradigm and investigated its relationship to rs686/A at DRD1 (associated with increased gene expression) and rs1800497/T at DRD2 (associated with reduced D2 receptor availability). Even though our sample (N = 264) was relatively young (18–40 years), we found that proactive inhibition improves the ability to withhold erroneous responses in older participants (p = 0.002) and those with lower fluid intelligence scores (p < 0.001), indicating that proactive inhibition is likely a naturally occurring compensatory mechanism. Critically, we found that a polygenic risk score consisting of the number of rs686 A and rs1800497 T alleles predicts higher engagement of proactive inhibition (p = 0.040), even after controlling for age (p = 0.011). Furthermore, age seemed to magnify these genetic effects (p < 0.001). This suggests that the extent to which proactive inhibition is engaged depends on increased dopamine D1 and decreased D2 neurotransmission. These results provide important considerations for future work investigating disorders of the dopaminergic system. Nathan D. Beu, Nicholas R. Burns, Irina Baetu https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14323?af=R European Journal of Neuroscience Polymorphisms in dopaminergic genes predict proactive processes of response inhibition

Here, we report that a genetic risk score (uGRS) combining rs686/A and rs1800497/T influences post‐error slowing (PES), a measure of proactive response inhibition, in a Go/No‐Go task. Even in our young sample (N = 265; age: M = 24.6, range = 18–40), age mediates the relationship between uGRS and PES; a higher uGRS seems to allow older subjects to engage proactive inhibition significantly more than young subjects to compensate for age‐related decay in the ability to withhold a prepotent response.

 

Abstract

The ability to inhibit a prepared emotional or motor action is difficult but critical to everyday functioning. It is well‐established that response inhibition relies on the dopaminergic system in the basal ganglia. However, response inhibition is often measured imprecisely due to a process which slows our responses and increases subsequent inhibition success known as proactive inhibition. As the role of the dopamine system in proactive inhibition is unclear, we investigated the contribution of dopaminergic genes to proactive inhibition. We operationalised proactive inhibition as slower responses after failures to inhibit a response in a Go/No‐Go paradigm and investigated its relationship to rs686/A at DRD1 (associated with increased gene expression) and rs1800497/T at DRD2 (associated with reduced D2 receptor availability). Even though our sample (N = 264) was relatively young (18–40 years), we found that proactive inhibition improves the ability to withhold erroneous responses in older participants (p = 0.002) and those with lower fluid intelligence scores (p < 0.001), indicating that proactive inhibition is likely a naturally occurring compensatory mechanism. Critically, we found that a polygenic risk score consisting of the number of rs686 A and rs1800497 T alleles predicts higher engagement of proactive inhibition (p = 0.040), even after controlling for age (p = 0.011). Furthermore, age seemed to magnify these genetic effects (p < 0.001). This suggests that the extent to which proactive inhibition is engaged depends on increased dopamine D1 and decreased D2 neurotransmission. These results provide important considerations for future work investigating disorders of the dopaminergic system.

European Journal of Neuroscience, EarlyView. Polymorphisms in dopaminergic genes predict proactive processes of response inhibition doi:10.1111/ejn.14323 European Journal of Neuroscience 2019-01-09T12:00:00-08:00 European Journal of Neuroscience 10.1111/ejn.14323 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14323?af=R RESEARCH REPORT Profiles of Women in Science: Prof. Catharine Winstanley of the University of British Columbia Dana L. Helmreich, The EJN Diversity, Inclusion Initiative https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14336?af=R European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. Profiles of Women in Science: Prof. Catharine Winstanley of the University of British Columbia doi:10.1111/ejn.14336 European Journal of Neuroscience 2019-01-07T06:24:57-08:00 European Journal of Neuroscience 10.1111/ejn.14336 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14336?af=R Editorial The COMT Val158Met polymorphism does not modulate the after‐effect of tDCS on working memory Individual differences in dopamine activity may impact the effects that transcranial direct current stimulation (tDCS) over prefrontal cortex has on cognition. However, in the present study we found no evidence suggesting that the effect of offline tDCS, that is stimulation prior to the critical task, is modulated by differences in the COMT polymorphism, which influences prefrontal dopamine activity. Taken together with previous findings, this suggests that dopamine may differently impact tDCS overlapping with vs. prior to the critical task. Abstract Transcranial direct current stimulation (tDCS) can alter cortical excitability, neural plasticity, and cognitive‐behavioral performance; however, its effects are known to vary across studies. A partial account of this variability relates to individual differences in dopamine function. Indeed, dopaminergic manipulations alter the physiological and cognitive‐behavioral effects of tDCS, and gene polymorphisms related to dopamine have predicted individual response to online tDCS (i.e., stimulation overlapping with the critical task). Notably, the role of individual differences in dopamine has not yet been properly assessed in the effect of offline tDCS (i.e., stimulation prior to the critical task). We investigated if and how the COMT Val158Met polymorphism (rs4680) modulates the after‐effect of prefrontal tDCS on verbal working memory (WM). One hundred and thirty‐nine participants were genotyped for the COMT Val158Met polymorphism and received anodal‐over‐left, cathodal‐over‐right (AL‐CR), cathodal‐over‐left, anodal‐over‐right (CL‐AR), or sham stimulation over the dorsolateral prefrontal cortex in a between‐subjects, pretest–posttest study design. WM was assessed using the N‐back task. The results provide no evidence that the COMT polymorphism impacts the after‐effect of prefrontal tDCS on WM. Taken together with previous findings on dopamine and tDCS interactions, the results of the present study suggest that (a) indirect markers of dopamine (such as COMT) are differently related to online and offline effects of tDCS, and (b) findings from studies involving pharmacological manipulation should be generalized with caution to findings of inter‐individual differences. In sum, we argue that state (i.e., a manipulation of) and trait (i.e., baseline) differences in dopamine may exert different effects on online and offline tDCS. Bryant J. Jongkees, Alexandra A. Loseva, Fatemeh B. Yavari, Michael A. Nitsche, Lorenza S. Colzato https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14261?af=R European Journal of Neuroscience The COMT Val158Met polymorphism does not modulate the after‐effect of tDCS on working memory

Individual differences in dopamine activity may impact the effects that transcranial direct current stimulation (tDCS) over prefrontal cortex has on cognition. However, in the present study we found no evidence suggesting that the effect of offline tDCS, that is stimulation prior to the critical task, is modulated by differences in the COMT polymorphism, which influences prefrontal dopamine activity. Taken together with previous findings, this suggests that dopamine may differently impact tDCS overlapping with vs. prior to the critical task.

 

Abstract

Transcranial direct current stimulation (tDCS) can alter cortical excitability, neural plasticity, and cognitive‐behavioral performance; however, its effects are known to vary across studies. A partial account of this variability relates to individual differences in dopamine function. Indeed, dopaminergic manipulations alter the physiological and cognitive‐behavioral effects of tDCS, and gene polymorphisms related to dopamine have predicted individual response to online tDCS (i.e., stimulation overlapping with the critical task). Notably, the role of individual differences in dopamine has not yet been properly assessed in the effect of offline tDCS (i.e., stimulation prior to the critical task). We investigated if and how the COMT Val158Met polymorphism (rs4680) modulates the after‐effect of prefrontal tDCS on verbal working memory (WM). One hundred and thirty‐nine participants were genotyped for the COMT Val158Met polymorphism and received anodal‐over‐left, cathodal‐over‐right (AL‐CR), cathodal‐over‐left, anodal‐over‐right (CL‐AR), or sham stimulation over the dorsolateral prefrontal cortex in a between‐subjects, pretest–posttest study design. WM was assessed using the N‐back task. The results provide no evidence that the COMT polymorphism impacts the after‐effect of prefrontal tDCS on WM. Taken together with previous findings on dopamine and tDCS interactions, the results of the present study suggest that (a) indirect markers of dopamine (such as COMT) are differently related to online and offline effects of tDCS, and (b) findings from studies involving pharmacological manipulation should be generalized with caution to findings of inter‐individual differences. In sum, we argue that state (i.e., a manipulation of) and trait (i.e., baseline) differences in dopamine may exert different effects on online and offline tDCS.

European Journal of Neuroscience, EarlyView. The COMT Val158Met polymorphism does not modulate the after‐effect of tDCS on working memory doi:10.1111/ejn.14261 European Journal of Neuroscience 2019-01-06T11:38:32-08:00 European Journal of Neuroscience 10.1111/ejn.14261 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14261?af=R RESEARCH REPORT Automatic detection of violations of statistical regularities in the periphery is affected by the focus of spatial attention: A visual mismatch negativity study Visual stimuli in close proximity to a continuously attended field elicited larger visual mismatch negativity (vMMN) than similar stimuli farther away from the stimulus field. Also, in case of close proximity, vMMN was followed by a posterior positivity. According to these results, spatial attention modulates vMMN and is capable of initiating further deviant processing. Abstract We investigated the effect of spatial attention on an event‐related potential signature of automatic detection of violations of statistical regularities, namely, the visual mismatch negativity (vMMN). To vary the task‐field and the location of vMMN‐related stimulation, in the attentional field the stimuli of a tracking task with a steady and a moving (target) bar were presented. The target stimuli of the task appeared either relatively close or far from a passive (task‐irrelevant) oddball or equiprobable sequence at the lower part of the screen. Stimuli of the oddball sequence were shapes tilted either 45° (standard, p = 0.8) or 135° (deviant, p = 0.2), while the equiprobable sequence consisted of additional three shapes with identical number of lines to the oddball stimuli. Deviant stimuli in close proximity to a continuously attended field elicited larger vMMN than similar stimuli farther away from the stimulus field. In the condition with a smaller distance between the field of the tracking task and the vMMN‐related field, the deviant stimuli and the vMMN was followed by a posterior positivity. According to these results, spatial attention modulates vMMN and is capable of initiating further processing of the deviant stimuli. Domonkos File, István Czigler https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14306?af=R European Journal of Neuroscience Automatic detection of violations of statistical regularities in the periphery is affected by the focus of spatial attention: A visual mismatch negativity study

Visual stimuli in close proximity to a continuously attended field elicited larger visual mismatch negativity (vMMN) than similar stimuli farther away from the stimulus field. Also, in case of close proximity, vMMN was followed by a posterior positivity. According to these results, spatial attention modulates vMMN and is capable of initiating further deviant processing.

 

Abstract

We investigated the effect of spatial attention on an event‐related potential signature of automatic detection of violations of statistical regularities, namely, the visual mismatch negativity (vMMN). To vary the task‐field and the location of vMMN‐related stimulation, in the attentional field the stimuli of a tracking task with a steady and a moving (target) bar were presented. The target stimuli of the task appeared either relatively close or far from a passive (task‐irrelevant) oddball or equiprobable sequence at the lower part of the screen. Stimuli of the oddball sequence were shapes tilted either 45° (standard, p = 0.8) or 135° (deviant, p = 0.2), while the equiprobable sequence consisted of additional three shapes with identical number of lines to the oddball stimuli. Deviant stimuli in close proximity to a continuously attended field elicited larger vMMN than similar stimuli farther away from the stimulus field. In the condition with a smaller distance between the field of the tracking task and the vMMN‐related field, the deviant stimuli and the vMMN was followed by a posterior positivity. According to these results, spatial attention modulates vMMN and is capable of initiating further processing of the deviant stimuli.

European Journal of Neuroscience, EarlyView. Automatic detection of violations of statistical regularities in the periphery is affected by the focus of spatial attention: A visual mismatch negativity study doi:10.1111/ejn.14306 European Journal of Neuroscience 2019-01-06T11:34:25-08:00 European Journal of Neuroscience 10.1111/ejn.14306 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14306?af=R RESEARCH REPORT Re‐fixation and perseveration patterns in neglect patients during free visual exploration The re‐fixation and perseveration rate in patients with left‐sided visual neglect during a free visual exploration task of naturalistic pictures was investigated. Neglect patients tended to re‐fixate locations within the ipsilesional hemispace, and they showed an overall higher rate of perseverative fixations than healthy controls. The results of this study thus further elucidate the mechanisms leading to perseverative behavior in neglect patients. Abstract The literature suggests that neglect patients not only show impairments in directing attention toward the left, contralesional space, but also present with perseverative behavior. Moreover, previous studies described re‐fixations during visual search tasks, and interpreted this finding as an impairment of spatial working memory. The aim of the present study was to study re‐fixations and perseverations (i.e., recurrent re‐fixations to same locations) during free visual exploration, a task with high ecological validity. We hypothesized that: (1) neglect patient would perform re‐fixations more frequently than healthy controls within the right hemispace; and, (2) the re‐fixation behavior of neglect patients would be characterized by perseverative fixations. To test these hypotheses, we assessed 22 neglect patients and 23 healthy controls, measuring their eye movements during free exploration of naturalistic pictures. The results showed that neglect patients tend to re‐fixate locations within the ipsilesional hemispace when they freely explore naturalistic pictures. Importantly, the saliency of discrete locations within the pictures has a stronger influence on fixation behavior within the contralesional than within the ipsilesional hemispace in neglect patients. Finally, the results indicated that, for re‐fixations, saliency plays a more important role within the contralesional than the ipsilesional hemispace. Moreover, we found evidence that re‐fixation behavior of neglect patients is characterized by frequent recurrent re‐fixations back to the same spatial locations which may be interpreted as perseverations. Hence, with the present study, we could better elucidate the mechanism leading to re‐fixations and perseverative behavior during free visual exploration in neglect patients. Rebecca E. Paladini, Patric Wyss, Brigitte C. Kaufmann, Prabitha Urwyler, Tobias Nef, Dario Cazzoli, Thomas Nyffeler, René M. Müri https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14309?af=R European Journal of Neuroscience Re‐fixation and perseveration patterns in neglect patients during free visual exploration

The re‐fixation and perseveration rate in patients with left‐sided visual neglect during a free visual exploration task of naturalistic pictures was investigated. Neglect patients tended to re‐fixate locations within the ipsilesional hemispace, and they showed an overall higher rate of perseverative fixations than healthy controls. The results of this study thus further elucidate the mechanisms leading to perseverative behavior in neglect patients.

 

Abstract

The literature suggests that neglect patients not only show impairments in directing attention toward the left, contralesional space, but also present with perseverative behavior. Moreover, previous studies described re‐fixations during visual search tasks, and interpreted this finding as an impairment of spatial working memory. The aim of the present study was to study re‐fixations and perseverations (i.e., recurrent re‐fixations to same locations) during free visual exploration, a task with high ecological validity. We hypothesized that: (1) neglect patient would perform re‐fixations more frequently than healthy controls within the right hemispace; and, (2) the re‐fixation behavior of neglect patients would be characterized by perseverative fixations. To test these hypotheses, we assessed 22 neglect patients and 23 healthy controls, measuring their eye movements during free exploration of naturalistic pictures. The results showed that neglect patients tend to re‐fixate locations within the ipsilesional hemispace when they freely explore naturalistic pictures. Importantly, the saliency of discrete locations within the pictures has a stronger influence on fixation behavior within the contralesional than within the ipsilesional hemispace in neglect patients. Finally, the results indicated that, for re‐fixations, saliency plays a more important role within the contralesional than the ipsilesional hemispace. Moreover, we found evidence that re‐fixation behavior of neglect patients is characterized by frequent recurrent re‐fixations back to the same spatial locations which may be interpreted as perseverations. Hence, with the present study, we could better elucidate the mechanism leading to re‐fixations and perseverative behavior during free visual exploration in neglect patients.

European Journal of Neuroscience, EarlyView. Re‐fixation and perseveration patterns in neglect patients during free visual exploration doi:10.1111/ejn.14309 European Journal of Neuroscience 2019-01-06T11:24:20-08:00 European Journal of Neuroscience 10.1111/ejn.14309 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14309?af=R RESEARCH REPORT Impaired cocaine‐induced behavioral plasticity in the male offspring of cocaine‐experienced sires Male first‐generation progeny of sires that chronically self‐administered cocaine show lower cocaine sensitivity and changes in histone post‐translational modifications in the nucleus accumbens. In contrast, second‐generation offspring of cocaine‐taking sires show unaltered cocaine self‐administration and cocaine behavioral sensitization. These data indicate that paternal cocaine exposure confers altered cocaine sensitivity in male offspring but not in subsequent generations. Abstract Our previous work indicated that male, but not female, offspring of cocaine‐experienced sires display blunted cocaine self‐administration. We extended this line of investigation to examine behavioral sensitization, a commonly used model of cocaine‐induced behavioral and neuronal plasticity. Results indicated that male, but not female, offspring of cocaine‐taking sires showed deficits in the ability of repeated systemic cocaine injections to induce augmented locomotor activity. The reduced cocaine sensitization phenotype in male progeny was associated with changes in histone post‐translational modifications, epigenetic processes that regulate gene expression by controlling the accessibility of genes to transcriptional machinery, in the nucleus accumbens of first‐generation male progeny. Thus, five histone post‐translational modifications were significantly altered in the male progeny of cocaine‐exposed sires. In contrast, self‐administration of nicotine was unaltered in male and female offspring suggesting that the intergenerational effects of paternal cocaine taking may be drug‐specific. Interestingly, the reduced sensitivity to cocaine previously observed in the male offspring of cocaine‐taking sires dissipated in the grand‐offspring. Both male and female grand‐progeny of cocaine‐exposed sires showed unaltered cocaine‐induced behavioral sensitization and cocaine self‐administration. Taken together, these findings indicate that paternal cocaine taking produces changes in multiple cocaine addiction‐related behaviors in male progeny, which do not persist beyond the first generation of offspring. Moreover, the altered sensitivity to cocaine in first‐generation male progeny of cocaine‐sired male offspring was associated with epigenetic modifications in the nucleus accumbens, a nucleus that plays a critical role in cocaine‐associated behavioral plasticity. Mathieu E. Wimmer, Fair M. Vassoler, Samantha L. White, Heath D. Schmidt, Simone Sidoli, Yumiao Han, Benjamin A. Garcia, R. Christopher Pierce https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14310?af=R European Journal of Neuroscience Impaired cocaine‐induced behavioral plasticity in the male offspring of cocaine‐experienced sires

Male first‐generation progeny of sires that chronically self‐administered cocaine show lower cocaine sensitivity and changes in histone post‐translational modifications in the nucleus accumbens. In contrast, second‐generation offspring of cocaine‐taking sires show unaltered cocaine self‐administration and cocaine behavioral sensitization. These data indicate that paternal cocaine exposure confers altered cocaine sensitivity in male offspring but not in subsequent generations.

 

Abstract

Our previous work indicated that male, but not female, offspring of cocaine‐experienced sires display blunted cocaine self‐administration. We extended this line of investigation to examine behavioral sensitization, a commonly used model of cocaine‐induced behavioral and neuronal plasticity. Results indicated that male, but not female, offspring of cocaine‐taking sires showed deficits in the ability of repeated systemic cocaine injections to induce augmented locomotor activity. The reduced cocaine sensitization phenotype in male progeny was associated with changes in histone post‐translational modifications, epigenetic processes that regulate gene expression by controlling the accessibility of genes to transcriptional machinery, in the nucleus accumbens of first‐generation male progeny. Thus, five histone post‐translational modifications were significantly altered in the male progeny of cocaine‐exposed sires. In contrast, self‐administration of nicotine was unaltered in male and female offspring suggesting that the intergenerational effects of paternal cocaine taking may be drug‐specific. Interestingly, the reduced sensitivity to cocaine previously observed in the male offspring of cocaine‐taking sires dissipated in the grand‐offspring. Both male and female grand‐progeny of cocaine‐exposed sires showed unaltered cocaine‐induced behavioral sensitization and cocaine self‐administration. Taken together, these findings indicate that paternal cocaine taking produces changes in multiple cocaine addiction‐related behaviors in male progeny, which do not persist beyond the first generation of offspring. Moreover, the altered sensitivity to cocaine in first‐generation male progeny of cocaine‐sired male offspring was associated with epigenetic modifications in the nucleus accumbens, a nucleus that plays a critical role in cocaine‐associated behavioral plasticity.

European Journal of Neuroscience, EarlyView. Impaired cocaine‐induced behavioral plasticity in the male offspring of cocaine‐experienced sires doi:10.1111/ejn.14310 European Journal of Neuroscience 2019-01-06T11:18:10-08:00 European Journal of Neuroscience 10.1111/ejn.14310 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14310?af=R RESEARCH REPORT Transcriptional control of synaptic components by the clock machinery Transcription factors from the molecular circadian clock regulate the expression of genes of multiple components of the synapse, the functional communication unit of the nervous system. Direct and indirect transcriptional regulation by the clock machinery of selected components such as neuropeptides, neurotransmitter regulators, vesicle proteins, receptors, transporters, channels, and adhesion and scaffolding molecules is reviewed for different brain areas. Abstract Circadian rhythms are generated in mammals by a central clock located in the suprachiasmatic nucleus of the hypothalamus, which regulates the homeostasis of many biological processes. At the molecular level, the regulation of circadian rhythms is under the control of transcriptional‐translational feedback loops composed of clock factors, including transcription factors. In the brain, synaptic plasticity has been shown to vary with a 24‐h rhythm. Also, when measured at a given time‐of‐day, synaptic plasticity has been observed to be disrupted by dysregulation of clock factors. This could suggest a regulation of synaptic functions by the clock machinery. Interestingly, many studies provide support for direct and indirect transcriptional regulation by core clock factors, including rhythmic gene expression, for a variety of synaptic components. Indeed, the gene of several neuropeptides, neurotransmitter regulators, receptors and transporters, ion channels, vesicle proteins, and adhesion and scaffolding molecules present evidence to be clock‐controlled. We here present, while considering different regions of the mammalian brain, an overview of the extent of the transcriptional control of synaptic components by the clock machinery. Lydia Hannou, Pierre‐Gabriel Roy, Maria Neus Ballester Roig, Valérie Mongrain https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14294?af=R European Journal of Neuroscience Transcriptional control of synaptic components by the clock machinery

Transcription factors from the molecular circadian clock regulate the expression of genes of multiple components of the synapse, the functional communication unit of the nervous system. Direct and indirect transcriptional regulation by the clock machinery of selected components such as neuropeptides, neurotransmitter regulators, vesicle proteins, receptors, transporters, channels, and adhesion and scaffolding molecules is reviewed for different brain areas.

 

Abstract

Circadian rhythms are generated in mammals by a central clock located in the suprachiasmatic nucleus of the hypothalamus, which regulates the homeostasis of many biological processes. At the molecular level, the regulation of circadian rhythms is under the control of transcriptional‐translational feedback loops composed of clock factors, including transcription factors. In the brain, synaptic plasticity has been shown to vary with a 24‐h rhythm. Also, when measured at a given time‐of‐day, synaptic plasticity has been observed to be disrupted by dysregulation of clock factors. This could suggest a regulation of synaptic functions by the clock machinery. Interestingly, many studies provide support for direct and indirect transcriptional regulation by core clock factors, including rhythmic gene expression, for a variety of synaptic components. Indeed, the gene of several neuropeptides, neurotransmitter regulators, receptors and transporters, ion channels, vesicle proteins, and adhesion and scaffolding molecules present evidence to be clock‐controlled. We here present, while considering different regions of the mammalian brain, an overview of the extent of the transcriptional control of synaptic components by the clock machinery.

European Journal of Neuroscience, EarlyView. Transcriptional control of synaptic components by the clock machinerydoi:10.1111/ejn.14294European Journal of Neuroscience2019-01-06T11:13:55-08:00European Journal of Neuroscience10.1111/ejn.14294 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14294?af=RSPECIAL ISSUE REVIEW Genetically engineered stem cell‐derived neurons can be rendered resistant to alpha‐synuclein aggregate pathology Abstract We discuss the implications of a recent study by Chen and collaborators which demonstrated that dopamine neurons derived from human pluripotent stem cells which had been genetically engineered to delete the alpha‐synuclein gene are resistant to the experimental induction of Lewy pathology (Chen et al., 2018). Neural transplants in Parkinson's disease patients can develop Lewy pathology over a decade after the graft surgery, and this pathology might compromise the long‐term survival and function of the grafted neurons. Therefore, the study by Chen et al has potential clinical implications where alpha‐synuclein null neurons might eventually be considered as possible donor cells in future intracerebral transplantation trials in Parkinson's disease. This article is protected by copyright. All rights reserved. Patrik Brundin, Gerhard A Coetzee https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14333?af=R

Abstract

We discuss the implications of a recent study by Chen and collaborators which demonstrated that dopamine neurons derived from human pluripotent stem cells which had been genetically engineered to delete the alpha‐synuclein gene are resistant to the experimental induction of Lewy pathology (Chen et al., 2018). Neural transplants in Parkinson's disease patients can develop Lewy pathology over a decade after the graft surgery, and this pathology might compromise the long‐term survival and function of the grafted neurons. Therefore, the study by Chen et al has potential clinical implications where alpha‐synuclein null neurons might eventually be considered as possible donor cells in future intracerebral transplantation trials in Parkinson's disease.

This article is protected by copyright. All rights reserved.

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. Genetically engineered stem cell‐derived neurons can be rendered resistant to alpha‐synuclein aggregate pathologydoi:10.1111/ejn.14333European Journal of Neuroscience2019-01-05T04:47:58-08:00European Journal of Neuroscience10.1111/ejn.14333 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14333?af=RFeatured Paper CommentarySleep and synaptic down‐selection Abstract The synaptic homeostasis hypothesis (SHY) proposes that sleep is an essential process needed by the brain to maintain the total amount of synaptic strength under control. SHY predicts that by the end of a waking day the synaptic connections of many neural circuits undergo a net increase in synaptic strength due to ongoing learning, which is mainly mediated by synaptic potentiation. Stronger synapses require more energy and supplies and are prone to saturation, creating the need for synaptic renormalization. Such renormalization should mainly occur during sleep, when the brain is disconnected from the environment and neural circuits can be broadly reactivated off‐line to undergo a systematic but specific synaptic down‐selection. In short, according to SHY sleep is the price to pay for waking plasticity, to avoid runaway potentiation, decreased signal‐to‐noise ratio, and impaired learning due to saturation. In this review we briefly discuss the rationale of the hypothesis and recent supportive ultrastructural evidence obtained in our laboratory. We then examine recent studies by other groups showing the causal role of cortical slow waves and hippocampal sharp waves/ripples in sleep‐dependent down‐selection of neural activity and synaptic strength. Finally, we discuss some of the molecular mechanisms that could mediate synaptic weakening during sleep. This article is protected by copyright. All rights reserved. Giulio Tononi, Chiara Cirelli https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14335?af=R

Abstract

The synaptic homeostasis hypothesis (SHY) proposes that sleep is an essential process needed by the brain to maintain the total amount of synaptic strength under control. SHY predicts that by the end of a waking day the synaptic connections of many neural circuits undergo a net increase in synaptic strength due to ongoing learning, which is mainly mediated by synaptic potentiation. Stronger synapses require more energy and supplies and are prone to saturation, creating the need for synaptic renormalization. Such renormalization should mainly occur during sleep, when the brain is disconnected from the environment and neural circuits can be broadly reactivated off‐line to undergo a systematic but specific synaptic down‐selection. In short, according to SHY sleep is the price to pay for waking plasticity, to avoid runaway potentiation, decreased signal‐to‐noise ratio, and impaired learning due to saturation. In this review we briefly discuss the rationale of the hypothesis and recent supportive ultrastructural evidence obtained in our laboratory. We then examine recent studies by other groups showing the causal role of cortical slow waves and hippocampal sharp waves/ripples in sleep‐dependent down‐selection of neural activity and synaptic strength. Finally, we discuss some of the molecular mechanisms that could mediate synaptic weakening during sleep.

This article is protected by copyright. All rights reserved.

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.Sleep and synaptic down‐selectiondoi:10.1111/ejn.14335European Journal of Neuroscience2019-01-05T04:43:55-08:00European Journal of Neuroscience10.1111/ejn.14335 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14335?af=RSpecial Issue Review Circadian Rhythm of Redox State Regulates Membrane Excitability in Hippocampal CA1 Neurons Abstract Behaviors, such as sleeping, foraging, and learning, are controlled by different regions of the rat brain, yet they occur rhythmically over the course of day and night. They are aligned adaptively with the day‐night cycle by an endogenous circadian clock in the suprachiasmatic nucleus (SCN), but local mechanisms of rhythmic control are not established. The SCN expresses a ~24‐h oscillation in reduction‐oxidation that modulates its own neuronal excitability. Could circadian redox oscillations control neuronal excitability elsewhere in the brain? We focused on the CA1 region of the rat hippocampus, which is known for integrating information as memories and where clock‐gene expression undergoes a circadian oscillation that is in anti‐phase to the SCN. Evaluating long‐term imaging of endogenous redox couples and biochemical determination of glutathiolation levels, we observed oscillations with an ~24 h period that is 180° out‐of‐phase to the SCN. Excitability of CA1 pyramidal neurons, primary hippocampal projection neurons, also exhibits a rhythm in resting membrane potential that is circadian time‐dependent and opposite from that of the SCN. The reducing reagent glutathione rapidly and reversibly depolarized the resting membrane potential of CA1 neurons; the magnitude is time‐of‐day‐dependent and, again, opposite from the SCN. These findings extend circadian redox regulation of neuronal excitability from the SCN to the hippocampus. Insights into this system contribute to understanding hippocampal circadian processes, such as learning and memory, seizure susceptibility, and memory loss with aging. This article is protected by copyright. All rights reserved. Ghazal Naseri Kouzehgarani, Mia Y. Bothwell, Martha U. Gillette https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14334?af=R

Abstract

Behaviors, such as sleeping, foraging, and learning, are controlled by different regions of the rat brain, yet they occur rhythmically over the course of day and night. They are aligned adaptively with the day‐night cycle by an endogenous circadian clock in the suprachiasmatic nucleus (SCN), but local mechanisms of rhythmic control are not established. The SCN expresses a ~24‐h oscillation in reduction‐oxidation that modulates its own neuronal excitability. Could circadian redox oscillations control neuronal excitability elsewhere in the brain? We focused on the CA1 region of the rat hippocampus, which is known for integrating information as memories and where clock‐gene expression undergoes a circadian oscillation that is in anti‐phase to the SCN. Evaluating long‐term imaging of endogenous redox couples and biochemical determination of glutathiolation levels, we observed oscillations with an ~24 h period that is 180° out‐of‐phase to the SCN. Excitability of CA1 pyramidal neurons, primary hippocampal projection neurons, also exhibits a rhythm in resting membrane potential that is circadian time‐dependent and opposite from that of the SCN. The reducing reagent glutathione rapidly and reversibly depolarized the resting membrane potential of CA1 neurons; the magnitude is time‐of‐day‐dependent and, again, opposite from the SCN. These findings extend circadian redox regulation of neuronal excitability from the SCN to the hippocampus. Insights into this system contribute to understanding hippocampal circadian processes, such as learning and memory, seizure susceptibility, and memory loss with aging.

This article is protected by copyright. All rights reserved.

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. Circadian Rhythm of Redox State Regulates Membrane Excitability in Hippocampal CA1 Neurons doi:10.1111/ejn.14334 European Journal of Neuroscience 2019-01-04T11:44:18-08:00 European Journal of Neuroscience 10.1111/ejn.14334 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14334?af=R Special Issue Article Circadian disruption and human health: A bidirectional relationship The relationship between circadian disruption and human health is bidirectional. Circadian dysfunction can either result from abnormal timing or decreased amplitude of circadian signals. This dysfunction is associated with an increased risk for neurodegenerative disease, cardiometabolic disease and malignancy. These disorders can in turn feedback and cause further circadian dysfunction. Further research is needed into the use of strategies to improve circadian health, in turn improving disease outcomes. This review highlights the importance of time across multiple aspects of medicine, and discusses the concept of a new field focused on these interactions: circadian medicine. Abstract Circadian rhythm disorders have been classically associated with disorders of abnormal timing of the sleep–wake cycle, however circadian dysfunction can play a role in a wide range of pathology, ranging from the increased risk for cardiometabolic disease and malignancy in shift workers, prompting the need for a new field focused on the larger concept of circadian medicine. The relationship between circadian disruption and human health is bidirectional, with changes in circadian amplitude often preceding the classical symptoms of neurodegenerative disorders. As our understanding of the importance of circadian dysfunction in disease grows, we need to develop better clinical techniques for identifying circadian rhythms and also develop circadian based strategies for disease management. Overall this review highlights the need to bring the concept of time to all aspects of medicine, emphasizing circadian medicine as a prime example of both personalized and precision medicine. Sabra M. Abbott, Roneil G. Malkani, Phyllis C. Zee https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14298?af=R European Journal of Neuroscience Circadian disruption and human health: A bidirectional relationship

The relationship between circadian disruption and human health is bidirectional. Circadian dysfunction can either result from abnormal timing or decreased amplitude of circadian signals. This dysfunction is associated with an increased risk for neurodegenerative disease, cardiometabolic disease and malignancy. These disorders can in turn feedback and cause further circadian dysfunction. Further research is needed into the use of strategies to improve circadian health, in turn improving disease outcomes. This review highlights the importance of time across multiple aspects of medicine, and discusses the concept of a new field focused on these interactions: circadian medicine.

 

Abstract

Circadian rhythm disorders have been classically associated with disorders of abnormal timing of the sleep–wake cycle, however circadian dysfunction can play a role in a wide range of pathology, ranging from the increased risk for cardiometabolic disease and malignancy in shift workers, prompting the need for a new field focused on the larger concept of circadian medicine. The relationship between circadian disruption and human health is bidirectional, with changes in circadian amplitude often preceding the classical symptoms of neurodegenerative disorders. As our understanding of the importance of circadian dysfunction in disease grows, we need to develop better clinical techniques for identifying circadian rhythms and also develop circadian based strategies for disease management. Overall this review highlights the need to bring the concept of time to all aspects of medicine, emphasizing circadian medicine as a prime example of both personalized and precision medicine.

European Journal of Neuroscience, EarlyView. Circadian disruption and human health: A bidirectional relationship doi:10.1111/ejn.14298 European Journal of Neuroscience 2019-01-03T03:07:17-08:00 European Journal of Neuroscience 10.1111/ejn.14298 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14298?af=R SPECIAL ISSUE REVIEW The overlooked aspect of excitotoxicity: Glutamate‐independent excitotoxicity in traumatic brain injuries In addition to glutamate‐induced excitotoxicity, there are glutamate‐independent mechanisms that cause the rapid calcium influx into the neuronal cytoplasm, evoking or contributing to excitotoxicity. This review focuses on the role of the glutamate‐independent excitotoxic mechanisms of the mechanosensitive response of NMDA receptors, mechanoporation of the cell membrane, ischemia, and the release of calcium from intracellular stores. Abstract Traumatic brain injury (TBI) is a leading major cause of morbidity and mortality in youth and individuals under 45 year age. A wide variety of cellular and molecular mechanisms have been identified contributing to the pathogenesis of TBI. A better understanding of the pathophysiology behind TBI is essential for providing more effective treatment. Excitotoxicity as one of the secondary molecular events is a major contributing factor in apoptosis and neuronal death following the initial injury in TBI. Excitotoxicity is the rapid overload and influx of calcium into the cell cytoplasm, activating a series of deleterious signaling cascades causing the cell to undergo apoptosis. Conventional understanding is that the rapid influx of calcium is initiated through glutamate release. However, there are overlooked glutamate‐independent mechanisms that cause the rapid calcium influx into the neuronal cytoplasm, evoking or contributing to excitotoxicity. Therefore, the focus of this review will be on the role of the glutamate‐independent excitotoxic mechanisms of the mechanosensitive response of NMDA receptors, mechanoporation of the cell membrane, ischemia, and the release of calcium from intracellular stores. In conclusion, the shear and stretch forces during a TBI event may result in the mechanosensitive activation of NMDA receptors which contribute to glutamate‐independent excitotoxicity. Joel Tehse, Changiz Taghibiglou https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14307?af=R European Journal of Neuroscience The overlooked aspect of excitotoxicity: Glutamate‐independent excitotoxicity in traumatic brain injuries

In addition to glutamate‐induced excitotoxicity, there are glutamate‐independent mechanisms that cause the rapid calcium influx into the neuronal cytoplasm, evoking or contributing to excitotoxicity. This review focuses on the role of the glutamate‐independent excitotoxic mechanisms of the mechanosensitive response of NMDA receptors, mechanoporation of the cell membrane, ischemia, and the release of calcium from intracellular stores.

 

Abstract

Traumatic brain injury (TBI) is a leading major cause of morbidity and mortality in youth and individuals under 45 year age. A wide variety of cellular and molecular mechanisms have been identified contributing to the pathogenesis of TBI. A better understanding of the pathophysiology behind TBI is essential for providing more effective treatment. Excitotoxicity as one of the secondary molecular events is a major contributing factor in apoptosis and neuronal death following the initial injury in TBI. Excitotoxicity is the rapid overload and influx of calcium into the cell cytoplasm, activating a series of deleterious signaling cascades causing the cell to undergo apoptosis. Conventional understanding is that the rapid influx of calcium is initiated through glutamate release. However, there are overlooked glutamate‐independent mechanisms that cause the rapid calcium influx into the neuronal cytoplasm, evoking or contributing to excitotoxicity. Therefore, the focus of this review will be on the role of the glutamate‐independent excitotoxic mechanisms of the mechanosensitive response of NMDA receptors, mechanoporation of the cell membrane, ischemia, and the release of calcium from intracellular stores. In conclusion, the shear and stretch forces during a TBI event may result in the mechanosensitive activation of NMDA receptors which contribute to glutamate‐independent excitotoxicity.

European Journal of Neuroscience, EarlyView. The overlooked aspect of excitotoxicity: Glutamate‐independent excitotoxicity in traumatic brain injuries doi:10.1111/ejn.14307 European Journal of Neuroscience 2019-01-01T08:48:04-08:00 European Journal of Neuroscience 10.1111/ejn.14307 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14307?af=R REVIEW ARTICLE Using subjective expectations to model the neural underpinnings of proactive inhibition Proactive inhibition is the slowing down of behavioral responses just before a possible full stop. We have used a modified stop‐signal response task with fMRI measurements, that made it possible to use trail‐by‐trial variations in response times to model brain activation. Our results show that activation in brain areas related to inhibition are also active during anticipatory slowing‐down. Abstract Proactive inhibition – the anticipation of having to stop a response – relies on objective information contained in cue‐related contingencies in the environment, as well as on the subjective interpretation derived from these cues. To date, most studies of brain areas underlying proactive inhibition have exclusively considered the objective predictive value of environmental cues, by varying the probability of stop‐signals. However, by only taking into account the effect of different cues on brain activation, the subjective component of how cues affect behavior is ignored. We used a modified stop‐signal response task that includes a measurement for subjective expectation, to investigate the effect of this subjective interpretation. After presenting a cue indicating the probability that a stop‐signal will occur, subjects were asked whether they expected a stop‐signal to occur. Furthermore, response time was used to retrospectively model brain activation related to stop‐expectation. We found more activation during the cue period for 50% stop‐signal probability, when contrasting with 0%, in the mid and inferior frontal gyrus, inferior parietal lobe and putamen. When contrasting expected vs. unexpected trials, we found modest effects in the mid frontal gyrus, parietal, and occipital areas. With our third contrast, we modeled brain activation during the cue with trial‐by‐trial variances in response times. This yielded activation in the putamen, inferior parietal lobe, and mid frontal gyrus. Our study is the first to use the behavioral effects of proactive inhibition to identify the underlying brain regions, by employing an unbiased task‐design that temporally separates cue and response. Pascal Pas, Stefan Du Plessis, Hanna E. Munkhof, Thomas E. Gladwin, Matthijs Vink https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14308?af=R European Journal of Neuroscience Using subjective expectations to model the neural underpinnings of proactive inhibition

Proactive inhibition is the slowing down of behavioral responses just before a possible full stop. We have used a modified stop‐signal response task with fMRI measurements, that made it possible to use trail‐by‐trial variations in response times to model brain activation. Our results show that activation in brain areas related to inhibition are also active during anticipatory slowing‐down.

 

Abstract

Proactive inhibition – the anticipation of having to stop a response – relies on objective information contained in cue‐related contingencies in the environment, as well as on the subjective interpretation derived from these cues. To date, most studies of brain areas underlying proactive inhibition have exclusively considered the objective predictive value of environmental cues, by varying the probability of stop‐signals. However, by only taking into account the effect of different cues on brain activation, the subjective component of how cues affect behavior is ignored. We used a modified stop‐signal response task that includes a measurement for subjective expectation, to investigate the effect of this subjective interpretation. After presenting a cue indicating the probability that a stop‐signal will occur, subjects were asked whether they expected a stop‐signal to occur. Furthermore, response time was used to retrospectively model brain activation related to stop‐expectation. We found more activation during the cue period for 50% stop‐signal probability, when contrasting with 0%, in the mid and inferior frontal gyrus, inferior parietal lobe and putamen. When contrasting expected vs. unexpected trials, we found modest effects in the mid frontal gyrus, parietal, and occipital areas. With our third contrast, we modeled brain activation during the cue with trial‐by‐trial variances in response times. This yielded activation in the putamen, inferior parietal lobe, and mid frontal gyrus. Our study is the first to use the behavioral effects of proactive inhibition to identify the underlying brain regions, by employing an unbiased task‐design that temporally separates cue and response.

European Journal of Neuroscience, EarlyView. Using subjective expectations to model the neural underpinnings of proactive inhibition doi:10.1111/ejn.14308 European Journal of Neuroscience 2019-01-01T08:44:10-08:00 European Journal of Neuroscience 10.1111/ejn.14308 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14308?af=R RESEARCH REPORT Impulsivity trait and proactive cognitive control: An fMRI study Motor impulsivity scores positively correlates with the activation of left sensorimotor cortices, inferior and superior parietal lobule. The correlation between motor impulsivity with sensory motor cortices activation can be interpreted as a disinhibition of the motor system, whereas inferior and superior parietal lobule activations could reflect a compensatory proactive control mechanism. Abstract The ability to flexibly regulate our behavior is a fundamental feature of human cognition and requires efficient functioning of cognitive control. During movement preparation, proactive inhibitory control plays a crucial role in regulating the excitatory activity carried out by alertness. The balance between alertness and proactive inhibition could be altered in people with motor impulsivity trait, determining the typical failure in the inhibition of prepotent motor responses. To test this hypothesis, 36 young adults were administered the Barratt Impulsiveness Scale to assess motor impulsivity trait and underwent fMRI acquisition during the execution of an event‐related Go/Nogo task. To investigate motor preparation processes, we analyzed the “readiness” period, in which subjects were waiting and preparing for the upcoming stimulus (Go or Nogo). We found a positive significant correlation between motor impulsivity scores and the activation of left sensorimotor cortices. This result indicates that motor impulsivity trait might be associated with a disinhibition of the motor system, characterized by a diminished reactivity threshold and a reduced control over covert urges. Furthermore, we observed a positive significant correlation between motor impulsivity scores and the activation in left inferior and superior parietal lobule, which might be related to a more pronounced proactive control, probably reflecting a compensatory mechanism implemented by participants with a higher degree of motor impulsivity trait to reach a correct inhibition. Current findings provide a rationale for further studies aiming to better understand proactive control functioning in healthy impulsive subjects and under clinical conditions. Gioele Gavazzi, Arianna Rossi, Stefano Orsolini, Stefano Diciotti, Fabio Giovannelli, Emilia Salvadori, Leonardo Pantoni, Mario Mascalchi, Maria Pia Viggiano https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14301?af=R European Journal of Neuroscience Impulsivity trait and proactive cognitive control: An fMRI study

Motor impulsivity scores positively correlates with the activation of left sensorimotor cortices, inferior and superior parietal lobule. The correlation between motor impulsivity with sensory motor cortices activation can be interpreted as a disinhibition of the motor system, whereas inferior and superior parietal lobule activations could reflect a compensatory proactive control mechanism.

 

Abstract

The ability to flexibly regulate our behavior is a fundamental feature of human cognition and requires efficient functioning of cognitive control. During movement preparation, proactive inhibitory control plays a crucial role in regulating the excitatory activity carried out by alertness. The balance between alertness and proactive inhibition could be altered in people with motor impulsivity trait, determining the typical failure in the inhibition of prepotent motor responses. To test this hypothesis, 36 young adults were administered the Barratt Impulsiveness Scale to assess motor impulsivity trait and underwent fMRI acquisition during the execution of an event‐related Go/Nogo task. To investigate motor preparation processes, we analyzed the “readiness” period, in which subjects were waiting and preparing for the upcoming stimulus (Go or Nogo). We found a positive significant correlation between motor impulsivity scores and the activation of left sensorimotor cortices. This result indicates that motor impulsivity trait might be associated with a disinhibition of the motor system, characterized by a diminished reactivity threshold and a reduced control over covert urges. Furthermore, we observed a positive significant correlation between motor impulsivity scores and the activation in left inferior and superior parietal lobule, which might be related to a more pronounced proactive control, probably reflecting a compensatory mechanism implemented by participants with a higher degree of motor impulsivity trait to reach a correct inhibition. Current findings provide a rationale for further studies aiming to better understand proactive control functioning in healthy impulsive subjects and under clinical conditions.

European Journal of Neuroscience, EarlyView. Impulsivity trait and proactive cognitive control: An fMRI study doi:10.1111/ejn.14301 European Journal of Neuroscience 2019-01-01T08:34:05-08:00 European Journal of Neuroscience 10.1111/ejn.14301 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14301?af=R SHORT COMMUNICATION Genetically engineered animal models of Parkinson's disease: From worm to rodent Play your cards right: the strengths and limitations of genetically modified animal models of Parkinson's disease. Abstract Parkinson's disease (PD) is a progressive neurological disorder characterised by aberrant accumulation of insoluble proteins, including alpha‐synuclein, and a loss of dopaminergic neurons in the substantia nigra. The extended neurodegeneration leads to a drop of striatal dopamine levels responsible for disabling motor and non‐motor impairments. Although the causes of the disease remain unclear, it is well accepted among the scientific community that the disorder may also have a genetic component. For that reason, the number of genetically engineered animal models has greatly increased over the past two decades, ranging from invertebrates to more complex organisms such as mice and rats. This trend is growing as new genetic variants associated with the disease are discovered. The EU Joint Programme – Neurodegenerative Disease Research (JPND) has promoted the creation of an online database aiming at summarising the different features of experimental models of Parkinson's disease. This review discusses available genetic models of PD and the extent to which they adequately mirror the human pathology and reflects on future development and uses of genetically engineered experimental models for the study of PD. Ludivine S. Breger, Marie T. Fuzzati Armentero https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14300?af=R European Journal of Neuroscience Genetically engineered animal models of Parkinson's disease: From worm to rodent

Play your cards right: the strengths and limitations of genetically modified animal models of Parkinson's disease.

 

Abstract

Parkinson's disease (PD) is a progressive neurological disorder characterised by aberrant accumulation of insoluble proteins, including alpha‐synuclein, and a loss of dopaminergic neurons in the substantia nigra. The extended neurodegeneration leads to a drop of striatal dopamine levels responsible for disabling motor and non‐motor impairments. Although the causes of the disease remain unclear, it is well accepted among the scientific community that the disorder may also have a genetic component. For that reason, the number of genetically engineered animal models has greatly increased over the past two decades, ranging from invertebrates to more complex organisms such as mice and rats. This trend is growing as new genetic variants associated with the disease are discovered. The EU Joint Programme – Neurodegenerative Disease Research (JPND) has promoted the creation of an online database aiming at summarising the different features of experimental models of Parkinson's disease. This review discusses available genetic models of PD and the extent to which they adequately mirror the human pathology and reflects on future development and uses of genetically engineered experimental models for the study of PD.

European Journal of Neuroscience, EarlyView. Genetically engineered animal models of Parkinson's disease: From worm to rodent doi:10.1111/ejn.14300 European Journal of Neuroscience 2018-12-27T10:36:22-08:00 European Journal of Neuroscience 10.1111/ejn.14300 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14300?af=R SPECIAL ISSUE REVIEW Metabolic rhythms: A framework for coordinating cellular function Yeast grown at high density under aerobic conditions undergo short period oscillations in oxygen consumption that coordinate a number of metabolic and cellular processes. Although yeast are not known to have a clock transcription‐translation feedback loop; these rhythms share a number of characteristics with 12 and 24 hr rhythms in other eukaryotes. This article reviews literature on the yeast respiratory oscillation and highlights features that are likely to underpin biological oscillations of multiple periods. Abstract Circadian clocks are widespread among eukaryotes and generally involve feedback loops coupled with metabolic processes and redox balance. The organising power of these oscillations has not only allowed organisms to anticipate day–night cycles, but also acts to temporally compartmentalise otherwise incompatible processes, enhance metabolic efficiency, make the system more robust to noise and propagate signals among cells. While daily rhythms and the function of the circadian transcription‐translation loop have been the subject of extensive research over the past four decades, cycles of shorter period and respiratory oscillations, with which they are intertwined, have received less attention. Here, we describe features of yeast respiratory oscillations, which share many features with daily and 12 hr cellular oscillations in animal cells. This relatively simple system enables the analysis of dynamic rhythmic changes in metabolism, independent of cellular oscillations that are a product of the circadian transcription‐translation feedback loop. Knowledge gained from studying ultradian oscillations in yeast will lead to a better understanding of the basic mechanistic principles and evolutionary origins of oscillatory behaviour among eukaryotes. Helen C. Causton https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14296?af=R European Journal of Neuroscience Metabolic rhythms: A framework for coordinating cellular function

Yeast grown at high density under aerobic conditions undergo short period oscillations in oxygen consumption that coordinate a number of metabolic and cellular processes. Although yeast are not known to have a clock transcription‐translation feedback loop; these rhythms share a number of characteristics with 12 and 24 hr rhythms in other eukaryotes. This article reviews literature on the yeast respiratory oscillation and highlights features that are likely to underpin biological oscillations of multiple periods.

 

Abstract

Circadian clocks are widespread among eukaryotes and generally involve feedback loops coupled with metabolic processes and redox balance. The organising power of these oscillations has not only allowed organisms to anticipate day–night cycles, but also acts to temporally compartmentalise otherwise incompatible processes, enhance metabolic efficiency, make the system more robust to noise and propagate signals among cells. While daily rhythms and the function of the circadian transcription‐translation loop have been the subject of extensive research over the past four decades, cycles of shorter period and respiratory oscillations, with which they are intertwined, have received less attention. Here, we describe features of yeast respiratory oscillations, which share many features with daily and 12 hr cellular oscillations in animal cells. This relatively simple system enables the analysis of dynamic rhythmic changes in metabolism, independent of cellular oscillations that are a product of the circadian transcription‐translation feedback loop. Knowledge gained from studying ultradian oscillations in yeast will lead to a better understanding of the basic mechanistic principles and evolutionary origins of oscillatory behaviour among eukaryotes.

European Journal of Neuroscience, EarlyView. Metabolic rhythms: A framework for coordinating cellular function doi:10.1111/ejn.14296 European Journal of Neuroscience 2018-12-27T10:29:07-08:00 European Journal of Neuroscience 10.1111/ejn.14296 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14296?af=R SPECIAL ISSUE REVIEW Neural coding of the sound envelope is changed in the inferior colliculus immediately following acoustic trauma We quantified the effects of acute acoustic trauma on encoding of amplitude modulations in the guinea pig inferior colliculus. Recording sites tuned below the exposure frequency showed enhanced temporal coding of amplitude modulations, whereas higher frequency sites showed diminished temporal coding. Temporal modulation transfer functions became more low‐pass shaped following acoustic trauma. Abstract Sensorineural hearing loss is often accompanied by difficulties with understanding speech in fluctuating backgrounds, suggesting that neural coding of complex sound features, such as the sound envelope, is impaired. Here, we studied how temporal and rate coding of the envelope is affected in the inferior colliculus immediately after acoustic trauma. Neural activity in response to amplitude‐modulated noise was recorded from the inferior colliculus of the guinea pig, before and immediately after a 1‐hr 11‐kHz acoustic trauma. Units with a characteristic frequency (CF) below the trauma frequency (<11 kHz) showed increased response gains, a measure for temporal coding of the sound envelope, especially at low modulation frequencies (≤128 Hz). Units with a CF > 11 kHz, which had large acoustic trauma‐induced threshold shifts, had decreased response gains to amplitude‐modulated noise. Shapes of temporal modulation transfer functions shifted toward a higher proportion of low‐pass shapes in low‐CF units, and to less band‐pass shapes in high‐CF units. Furthermore, driven firing rates decreased, especially at high modulation frequencies for high‐CF units. The observed changes occurred immediately following trauma and were thus a result of the immediate trauma‐induced damage to the auditory system. If also present in human subjects, reduced response gains in high‐frequency units could disrupt coding of consonants and consequently impair speech understanding in noisy environments. Moreover, the enhanced temporal coding by low‐CF units of the low modulation frequencies could overly amplify responses to low‐frequency noise, further deteriorating listening in noise. Amarins N. Heeringa, Pim van Dijk https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14299?af=R European Journal of Neuroscience Neural coding of the sound envelope is changed in the inferior colliculus immediately following acoustic trauma

We quantified the effects of acute acoustic trauma on encoding of amplitude modulations in the guinea pig inferior colliculus. Recording sites tuned below the exposure frequency showed enhanced temporal coding of amplitude modulations, whereas higher frequency sites showed diminished temporal coding. Temporal modulation transfer functions became more low‐pass shaped following acoustic trauma.

 

Abstract

Sensorineural hearing loss is often accompanied by difficulties with understanding speech in fluctuating backgrounds, suggesting that neural coding of complex sound features, such as the sound envelope, is impaired. Here, we studied how temporal and rate coding of the envelope is affected in the inferior colliculus immediately after acoustic trauma. Neural activity in response to amplitude‐modulated noise was recorded from the inferior colliculus of the guinea pig, before and immediately after a 1‐hr 11‐kHz acoustic trauma. Units with a characteristic frequency (CF) below the trauma frequency (<11 kHz) showed increased response gains, a measure for temporal coding of the sound envelope, especially at low modulation frequencies (≤128 Hz). Units with a CF > 11 kHz, which had large acoustic trauma‐induced threshold shifts, had decreased response gains to amplitude‐modulated noise. Shapes of temporal modulation transfer functions shifted toward a higher proportion of low‐pass shapes in low‐CF units, and to less band‐pass shapes in high‐CF units. Furthermore, driven firing rates decreased, especially at high modulation frequencies for high‐CF units. The observed changes occurred immediately following trauma and were thus a result of the immediate trauma‐induced damage to the auditory system. If also present in human subjects, reduced response gains in high‐frequency units could disrupt coding of consonants and consequently impair speech understanding in noisy environments. Moreover, the enhanced temporal coding by low‐CF units of the low modulation frequencies could overly amplify responses to low‐frequency noise, further deteriorating listening in noise.

European Journal of Neuroscience, EarlyView. Neural coding of the sound envelope is changed in the inferior colliculus immediately following acoustic trauma doi:10.1111/ejn.14299 European Journal of Neuroscience 2018-12-27T10:28:51-08:00 European Journal of Neuroscience 10.1111/ejn.14299 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14299?af=R RESEARCH REPORT Interferon‐γ Receptor 1 and GluR1 upregulated in motor neurons of symptomatic hSOD1G93A mice In this study, we examine a non‐canonical, neuron‐specific IFN‐gamma pathway in hSOD1G93A motor neurons. The upstream targets IFNGR1 and GluR1, subunits of Interferon‐Gamma receptor and AMPAR respectively, are upregulated in motor neurons of hSOD1G93A mice. In contrast, the expression of key downstream participants—Jak1, Stat1, and Protein Kinase A, are not enhanced. Functional studies of the pathway in vitro demonstrated neuronal damage most likely from calcium ion influx. Abstract Motor neurons are markedly vulnerable to excitotoxicity mostly by alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic receptor (AMPAR) stimulation and are principal targets in the neurodegenerative disease Amyotrophic Lateral Sclerosis. Interferon‐gamma (IFN‐γ), a pro‐inflammatory cytokine, can independently cause neuronal dysfunction by triggering calcium influx through a calcium‐permeable complex of IFN‐γ receptor 1(IFNGR1) subunit and AMPAR subunit GluR1. This receptor complex is formed via a non‐canonical neuron‐specific IFN‐γ pathway that involves Jak1/Stat1 and Protein Kinase A. In this study, we explore the expression of the pathway's participants for the first time in the hSOD1G93A Amyotrophic Lateral Sclerosis mouse model. Elevated IFNGR1 and GluR1 are detected in motor neurons of hSOD1G93A symptomatic mice ex vivo, unlike the downstream targets ‐ Jak1, Stat1, and Protein Kinase A. We, also, determine effects of IFN‐γ alone or in the presence of an excitotoxic agent, kainate, on motor neuron survival in vitro. IFN‐γ induces neuronal damage, but does not influence kainate‐mediated excitotoxicity. Increased IFNGR1 can most likely sensitize motor neurons to excitotoxic insults involving GluR1 and/or pathways mediated by IFN‐γ, thus, serving as a potential direct link between neurodegeneration and inflammation in Amyotrophic Lateral Sclerosis. Saikata Sengupta, Thanh Tu Le, Adam Adam, Vedrana Tadić, Beatrice Stubendorff, Silke Keiner, Linda Kloss, Tino Prell, Otto W. Witte, Julian Grosskreutz https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14276?af=R European Journal of Neuroscience Interferon‐γ Receptor 1 and GluR1 upregulated in motor neurons of symptomatic hSOD1G93A mice

In this study, we examine a non‐canonical, neuron‐specific IFN‐gamma pathway in hSOD1G93A motor neurons. The upstream targets IFNGR1 and GluR1, subunits of Interferon‐Gamma receptor and AMPAR respectively, are upregulated in motor neurons of hSOD1G93A mice. In contrast, the expression of key downstream participants—Jak1, Stat1, and Protein Kinase A, are not enhanced. Functional studies of the pathway in vitro demonstrated neuronal damage most likely from calcium ion influx.

 

Abstract

Motor neurons are markedly vulnerable to excitotoxicity mostly by alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic receptor (AMPAR) stimulation and are principal targets in the neurodegenerative disease Amyotrophic Lateral Sclerosis. Interferon‐gamma (IFN‐γ), a pro‐inflammatory cytokine, can independently cause neuronal dysfunction by triggering calcium influx through a calcium‐permeable complex of IFN‐γ receptor 1(IFNGR1) subunit and AMPAR subunit GluR1. This receptor complex is formed via a non‐canonical neuron‐specific IFN‐γ pathway that involves Jak1/Stat1 and Protein Kinase A. In this study, we explore the expression of the pathway's participants for the first time in the hSOD1G93A Amyotrophic Lateral Sclerosis mouse model. Elevated IFNGR1 and GluR1 are detected in motor neurons of hSOD1G93A symptomatic mice ex vivo, unlike the downstream targets ‐ Jak1, Stat1, and Protein Kinase A. We, also, determine effects of IFN‐γ alone or in the presence of an excitotoxic agent, kainate, on motor neuron survival in vitro. IFN‐γ induces neuronal damage, but does not influence kainate‐mediated excitotoxicity. Increased IFNGR1 can most likely sensitize motor neurons to excitotoxic insults involving GluR1 and/or pathways mediated by IFN‐γ, thus, serving as a potential direct link between neurodegeneration and inflammation in Amyotrophic Lateral Sclerosis.

European Journal of Neuroscience, EarlyView. Interferon‐γ Receptor 1 and GluR1 upregulated in motor neurons of symptomatic hSOD1G93A micedoi:10.1111/ejn.14276European Journal of Neuroscience2018-12-27T10:24:49-08:00European Journal of Neuroscience10.1111/ejn.14276 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14276?af=RRESEARCH REPORTDevelopment of the mammalian circadian clock Abstract The mammalian circadian system is composed of a central clock situated in the hypothalamic suprachiasmatic nucleus (SCN) and peripheral clocks of each tissue and organ in the body. While much has been learned about the pre‐ and postnatal development of the circadian system, there are still many unanswered questions about how and when cellular clocks start to tick and from the circadian system. Most SCN neurons contain a cell‐autonomous circadian clock with individual specific periodicity. Therefore, the network of cellular oscillators is critical for the coherent rhythm expression and orchestration of the peripheral clocks by the SCN. The SCN is the only circadian clock entrained by an environmental light–dark cycle. Photic entrainment starts postnatally, and the SCN starts to function gradually as a central clock that controls physiological and behavioral rhythms during postnatal development. The SCN exhibits circadian rhythms in clock gene expression from the embryonic stage throughout postnatal life and the rhythm phenotypes remain basically unchanged. However, the disappearance of coherent circadian rhythms in cryptochrome‐deficient SCN revealed changes in the SCN networks that occur in postnatal weeks 2–3. The SCN network consists of multiple clusters of cellular circadian rhythms that are differentially integrated by the vasoactive intestinal polypeptide and arginine vasopressin signaling depending on the period of postnatal development. This article is protected by copyright. All rights reserved. Sato Honma https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14318?af=R

Abstract

The mammalian circadian system is composed of a central clock situated in the hypothalamic suprachiasmatic nucleus (SCN) and peripheral clocks of each tissue and organ in the body. While much has been learned about the pre‐ and postnatal development of the circadian system, there are still many unanswered questions about how and when cellular clocks start to tick and from the circadian system.

Most SCN neurons contain a cell‐autonomous circadian clock with individual specific periodicity. Therefore, the network of cellular oscillators is critical for the coherent rhythm expression and orchestration of the peripheral clocks by the SCN. The SCN is the only circadian clock entrained by an environmental light–dark cycle. Photic entrainment starts postnatally, and the SCN starts to function gradually as a central clock that controls physiological and behavioral rhythms during postnatal development. The SCN exhibits circadian rhythms in clock gene expression from the embryonic stage throughout postnatal life and the rhythm phenotypes remain basically unchanged. However, the disappearance of coherent circadian rhythms in cryptochrome‐deficient SCN revealed changes in the SCN networks that occur in postnatal weeks 2–3. The SCN network consists of multiple clusters of cellular circadian rhythms that are differentially integrated by the vasoactive intestinal polypeptide and arginine vasopressin signaling depending on the period of postnatal development.

This article is protected by copyright. All rights reserved.

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.Development of the mammalian circadian clockdoi:10.1111/ejn.14318European Journal of Neuroscience2018-12-27T10:18:39-08:00European Journal of Neuroscience10.1111/ejn.14318 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14318?af=RSpecial Issue Review Weighting of neural prediction error by rhythmic complexity: a predictive coding account using Mismatch Negativity Abstract The human brain's ability to extract and encode temporal regularities and to predict the timing of upcoming events is critical for music and speech perception. This work addresses how these mechanisms deal with different levels of temporal complexity, here the number of distinct interval durations in rhythmic patterns. We use electroencephalography (EEG) to relate the mismatch negativity (MMN), a proxy of neural prediction error, to a measure of information content of rhythmic sequences, the Shannon entropy. Within each of three conditions, participants listened to repeatedly presented standard rhythms of 5 tones (four interonset intervals) and of a given level of entropy: zero (isochronous), medium‐entropy (two distinct interval durations), or high‐entropy (four distinct interval durations). Occasionally, the fourth tone was shifted forward in time by either 100 ms (small deviation), or 300 ms (large deviation). According to the predictive coding framework, high‐entropy stimuli are more difficult to model for the brain, resulting in less confident predictions and yielding a smaller prediction error for deviant sounds. Our results support this hypothesis, showing a gradual decrease in MMN amplitude as a function of entropy, but only for small timing deviants. For large timing deviants, in contrast, a modulation of activity in the opposite direction was observed for the earlier N1 component, known to also be sensitive to sudden changes in directed attention. Our results suggest the existence of a fine‐grained neural mechanism that weights neural prediction error to the complexity of rhythms and that mostly manifests in the absence of directed attention. This article is protected by copyright. All rights reserved. Massimo Lumaca, Niels Trusbak Haumann, Elvira Brattico, Manon Grube, Peter Vuust https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14329?af=R

Abstract

The human brain's ability to extract and encode temporal regularities and to predict the timing of upcoming events is critical for music and speech perception. This work addresses how these mechanisms deal with different levels of temporal complexity, here the number of distinct interval durations in rhythmic patterns. We use electroencephalography (EEG) to relate the mismatch negativity (MMN), a proxy of neural prediction error, to a measure of information content of rhythmic sequences, the Shannon entropy. Within each of three conditions, participants listened to repeatedly presented standard rhythms of 5 tones (four interonset intervals) and of a given level of entropy: zero (isochronous), medium‐entropy (two distinct interval durations), or high‐entropy (four distinct interval durations). Occasionally, the fourth tone was shifted forward in time by either 100 ms (small deviation), or 300 ms (large deviation). According to the predictive coding framework, high‐entropy stimuli are more difficult to model for the brain, resulting in less confident predictions and yielding a smaller prediction error for deviant sounds. Our results support this hypothesis, showing a gradual decrease in MMN amplitude as a function of entropy, but only for small timing deviants. For large timing deviants, in contrast, a modulation of activity in the opposite direction was observed for the earlier N1 component, known to also be sensitive to sudden changes in directed attention. Our results suggest the existence of a fine‐grained neural mechanism that weights neural prediction error to the complexity of rhythms and that mostly manifests in the absence of directed attention.

This article is protected by copyright. All rights reserved.

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. Weighting of neural prediction error by rhythmic complexity: a predictive coding account using Mismatch Negativitydoi:10.1111/ejn.14329European Journal of Neuroscience2018-12-27T08:10:39-08:00European Journal of Neuroscience10.1111/ejn.14329 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14329?af=RResearch Report Selectivity for mid‐level properties of faces and places in the fusiform face area and parahippocampal place area Abstract Regions in the ventral visual pathway, such as the fusiform face area (FFA) and parahippocampal place area (PPA), are selective for images from specific object categories. Yet images from different object categories differ in their image properties. To investigate how these image properties are represented in the FFA and PPA, we compared neural responses to locally‐scrambled images (in which mid‐level, spatial properties are preserved) and globally‐scrambled images (in which mid‐level, spatial properties are not preserved). There was a greater response in the FFA and PPA to images from the preferred category relative to their non‐preferred category for the scrambled conditions. However, there was a greater selectivity for locally‐scrambled compared to globally‐scrambled images. Next, we compared the magnitude of fMR adaptation to intact and scrambled images. fMR‐adaptation was evident to locally‐scrambled images from the preferred category. However, there was no adaptation to globally‐scrambled images from the preferred category. These results show that the selectivity to faces and places in the FFA and PPA is dependent on mid‐level properties of the image that are preserved by local scrambling. This article is protected by copyright. All rights reserved. David D. Coggan, Daniel H. Baker, Timothy J. Andrews https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14327?af=R

Abstract

Regions in the ventral visual pathway, such as the fusiform face area (FFA) and parahippocampal place area (PPA), are selective for images from specific object categories. Yet images from different object categories differ in their image properties. To investigate how these image properties are represented in the FFA and PPA, we compared neural responses to locally‐scrambled images (in which mid‐level, spatial properties are preserved) and globally‐scrambled images (in which mid‐level, spatial properties are not preserved). There was a greater response in the FFA and PPA to images from the preferred category relative to their non‐preferred category for the scrambled conditions. However, there was a greater selectivity for locally‐scrambled compared to globally‐scrambled images. Next, we compared the magnitude of fMR adaptation to intact and scrambled images. fMR‐adaptation was evident to locally‐scrambled images from the preferred category. However, there was no adaptation to globally‐scrambled images from the preferred category. These results show that the selectivity to faces and places in the FFA and PPA is dependent on mid‐level properties of the image that are preserved by local scrambling.

This article is protected by copyright. All rights reserved.

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. Selectivity for mid‐level properties of faces and places in the fusiform face area and parahippocampal place areadoi:10.1111/ejn.14327European Journal of Neuroscience2018-12-27T08:09:07-08:00European Journal of Neuroscience10.1111/ejn.14327 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14327?af=RResearch Report Impairments in gait kinematics and postural control may not correlate with dopamine transporter depletion in individuals with mild to moderate Parkinson's disease Abstract Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by the loss of dopamine, an important neurotransmitter involved in regulating movement. Nuclear medicine imaging methods such as single photon emission computed tomography (SPECT) combined with radiotracers can obtain the density of this neurotransmitter. This reduced density leads to classic PD symptoms, such as bradykinesia, tremor and stiffness, consequently affecting walking and postural control. The aim of this study was to verify the correlation between disorders of gait kinematics and postural instability with dopamine depletion in individuals with mild to moderate PD. This is a descriptive, observational cross‐sectional study. Subjects were assessed for spatiotemporal gait parameters by a three‐dimensional motion capture system, for postural control by stabilometry on a force plate. Dopamine depletion was verified through 99mTc‐TRODAT‐1 (SPECT‐CT) examination. The subjects were in the off‐stage of levodopa in all analysis. We evaluated 71 individuals, 32 with mild to moderate PD (HY 2 and 2.5) and 39 healthy individuals matched for gender, age, and height. There was a significant difference between the groups regarding the spatiotemporal variables of gait, as well as in the stabilometric variables. However, there was no correlation between these disturbances and the uptake values of 99mTc‐TRODAT‐1. The results indicate that there is no correlation between gait impairments and postural instability of individuals with mild to moderate PD and the dopaminergic depletion measured through the 99mTc‐TRODAT‐1 (SPECT‐CT). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved. Maria Eduarda Parcianello Cabeleira, Aline Souza Pagnussat, Alexandre Severo do Pinho, Ane Caroline Dotta Asquidamini, Ariane Bolla Freire, Brenda Tubelo Pereira, Carlos Roberto de Mello Rieder, Giulia Palermo Schifino, Luis Henrique Tieppo Fornari, Neivo da Silva, Philipe Souza Corrêa, Fernanda Cechetti https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14328?af=R

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by the loss of dopamine, an important neurotransmitter involved in regulating movement. Nuclear medicine imaging methods such as single photon emission computed tomography ( SPECT ) combined with radiotracers can obtain the density of this neurotransmitter. This reduced density leads to classic PD symptoms, such as bradykinesia, tremor and stiffness, consequently affecting walking and postural control. The aim of this study was to verify the correlation between disorders of gait kinematics and postural instability with dopamine depletion in individuals with mild to moderate PD . This is a descriptive, observational cross‐sectional study. Subjects were assessed for spatiotemporal gait parameters by a three‐dimensional motion capture system, for postural control by stabilometry on a force plate. Dopamine depletion was verified through 99mTc‐ TRODAT ‐1 ( SPECT CT ) examination. The subjects were in the off‐stage of levodopa in all analysis. We evaluated 71 individuals, 32 with mild to moderate PD ( HY 2 and 2.5) and 39 healthy individuals matched for gender, age, and height. There was a significant difference between the groups regarding the spatiotemporal variables of gait, as well as in the stabilometric variables. However, there was no correlation between these disturbances and the uptake values of 99mTc‐TRODAT‐1. The results indicate that there is no correlation between gait impairments and postural instability of individuals with mild to moderate PD and the dopaminergic depletion measured through the 99mTc‐TRODAT‐1 (SPECT‐CT).

This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. Impairments in gait kinematics and postural control may not correlate with dopamine transporter depletion in individuals with mild to moderate Parkinson's diseasedoi:10.1111/ejn.14328European Journal of Neuroscience2018-12-27T08:09:06-08:00European Journal of Neuroscience10.1111/ejn.14328 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14328?af=RResearch Report A Sam68‐dependent alternative splicing program shapes postsynaptic protein complexes Abstract Alternative splicing is one of the key mechanisms to increase the diversity of cellular transcriptomes, thereby expanding the coding capacity of the genome. This diversity is of particular importance in the nervous system with its elaborated cellular networks. Sam68, a member of the Signal Transduction Associated RNA‐binding (STAR) family of RNA‐binding proteins, is expressed in the developing and mature nervous system but its neuronal functions are poorly understood. Here, we perform genome‐wide mapping of the Sam68‐dependent alternative splicing program in mice. We find that Sam68 is required for the regulation of a set of alternative splicing events in pre‐mRNAs encoding several postsynaptic scaffolding molecules that are central to the function of GABAergic and glutamatergic synapses. These components include Collybistin (Arhgef9), Gephyrin (Gphn), and Densin‐180 (Lrrc7). Sam68‐regulated Lrrc7 variants engage in differential protein interactions with signalling proteins, thus, highlighting a contribution of the Sam68 splicing program to shaping synaptic complexes. These findings suggest an important role for Sam68‐dependent alternative splicing in the regulation of synapses in the central nervous system. This article is protected by copyright. All rights reserved. Harald Witte, Dietmar Schreiner, Peter Scheiffele https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14332?af=R

Abstract

Alternative splicing is one of the key mechanisms to increase the diversity of cellular transcriptomes, thereby expanding the coding capacity of the genome. This diversity is of particular importance in the nervous system with its elaborated cellular networks. Sam68, a member of the Signal Transduction Associated RNA‐binding (STAR) family of RNA‐binding proteins, is expressed in the developing and mature nervous system but its neuronal functions are poorly understood. Here, we perform genome‐wide mapping of the Sam68‐dependent alternative splicing program in mice. We find that Sam68 is required for the regulation of a set of alternative splicing events in pre‐mRNAs encoding several postsynaptic scaffolding molecules that are central to the function of GABAergic and glutamatergic synapses. These components include Collybistin (Arhgef9), Gephyrin (Gphn), and Densin‐180 (Lrrc7). Sam68‐regulated Lrrc7 variants engage in differential protein interactions with signalling proteins, thus, highlighting a contribution of the Sam68 splicing program to shaping synaptic complexes. These findings suggest an important role for Sam68‐dependent alternative splicing in the regulation of synapses in the central nervous system.

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European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. A Sam68‐dependent alternative splicing program shapes postsynaptic protein complexesdoi:10.1111/ejn.14332European Journal of Neuroscience2018-12-27T05:34:48-08:00European Journal of Neuroscience10.1111/ejn.14332 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14332?af=RResearch Report Multivariate fMRI pattern analysis of fear perception across modalities Abstract The emotional expression of fear can be processed through a number of modalities, and of varying forms, however, much of the functional imaging literature has centered on investigating fear as expressed through faces. Findings point to an active involvement of the amygdala, and remain fairly consistent in other studies of unimodal fear perception; however, few studies have looked at within‐subject cross‐modal responses to fear. Thus, we approached this inquiry by testing 30 healthy young adults with fast, high‐resolution fMRI, recording the neural responses of fear perception, as expressed through faces, bodies, prosody and vocalizations. The study was analyzed using a multivariate approach (multi‐voxel pattern analysis; MVPA) and yielded a significant distinction in the responses associated with the perception of fearful versus neutral emotions. Calculated weights highlighted areas in the amygdala and surrounding subcortical structures as contributing the greatest to the discrimination; however, a whole‐brain analysis was necessary to obtain above‐chance classification accuracy, suggesting that processing fear across modalities likely involves a broad, distributed network. Thus, our findings support a multivariate approach to studying a highly complex construct such as emotion, as it accounts for multiple voxels simultaneously and can accommodate the high subject‐level variability that oftentimes comes with studying emotion perception. This article is protected by copyright. All rights reserved. Jocelyne C. Whitehead, Jorge L. Armony https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14322?af=R

Abstract

The emotional expression of fear can be processed through a number of modalities, and of varying forms, however, much of the functional imaging literature has centered on investigating fear as expressed through faces. Findings point to an active involvement of the amygdala, and remain fairly consistent in other studies of unimodal fear perception; however, few studies have looked at within‐subject cross‐modal responses to fear. Thus, we approached this inquiry by testing 30 healthy young adults with fast, high‐resolution fMRI, recording the neural responses of fear perception, as expressed through faces, bodies, prosody and vocalizations. The study was analyzed using a multivariate approach (multi‐voxel pattern analysis; MVPA) and yielded a significant distinction in the responses associated with the perception of fearful versus neutral emotions. Calculated weights highlighted areas in the amygdala and surrounding subcortical structures as contributing the greatest to the discrimination; however, a whole‐brain analysis was necessary to obtain above‐chance classification accuracy, suggesting that processing fear across modalities likely involves a broad, distributed network. Thus, our findings support a multivariate approach to studying a highly complex construct such as emotion, as it accounts for multiple voxels simultaneously and can accommodate the high subject‐level variability that oftentimes comes with studying emotion perception.

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European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. Multivariate fMRI pattern analysis of fear perception across modalitiesdoi:10.1111/ejn.14322European Journal of Neuroscience2018-12-27T04:43:30-08:00European Journal of Neuroscience10.1111/ejn.14322 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14322?af=RShort Communication Feeding cycle alters the biophysics and molecular expression of voltage‐gated Na+ currents in rat hippocampal CA1 neurones Abstract The function of hippocampus as a hub for energy balance is a subject of broad and current interest. The present study aims at providing more evidence on this regard by addressing the effects of feeding cycle on the voltage‐gated sodium (Na+) currents of acutely isolated Wistar rat hippocampal CA1 neurones. Specifically, by applying patch clamp techniques (whole cell voltage clamp and single channel in inside‐out patches we assessed the influence of feeding and fasting conditions on the intrinsic biophysical properties of Na+ currents. Additionally, mass spectrometry and western blotting experiments were used to address the effect of feeding cycle over the Na+ channel population of the rat hippocampus. Na+ currents were recorded in neurones obtained from fed and fasted animals (here termed ‘fed neurones’ and ‘fasted neurones’, respectively). Whole cell Na+ currents of fed neurones, as compared to fasted neurones, showed increased mean maximum current density and a higher ‘window current’ amplitude. We demonstrate that these results are supported by an increased single channel Na+ conductance in fed neurones and, also, by a greater Nav1.2 channel density in plasma membrane‐enriched fractions of fed samples (but not in whole hippocampus preparations). These results imply fast variations on the biophysics and molecular expression of Na+ currents of rat hippocampal CA1 neurones, throughout the feeding cycle. Thus, one may expect a differentiated regulation of the intrinsic neuronal excitability, which may account for the role of the hippocampus as a processor of satiety information. This article is protected by copyright. All rights reserved. André E. P. Bastos, Pedro F. Costa, Suzy Varderidou‐Minasian, Maarten Altelaar, Pedro A. Lima https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14331?af=R

Abstract

The function of hippocampus as a hub for energy balance is a subject of broad and current interest. The present study aims at providing more evidence on this regard by addressing the effects of feeding cycle on the voltage‐gated sodium (Na+) currents of acutely isolated Wistar rat hippocampal CA1 neurones. Specifically, by applying patch clamp techniques (whole cell voltage clamp and single channel in inside‐out patches we assessed the influence of feeding and fasting conditions on the intrinsic biophysical properties of Na+ currents. Additionally, mass spectrometry and western blotting experiments were used to address the effect of feeding cycle over the Na+ channel population of the rat hippocampus. Na+ currents were recorded in neurones obtained from fed and fasted animals (here termed ‘fed neurones’ and ‘fasted neurones’, respectively). Whole cell Na+ currents of fed neurones, as compared to fasted neurones, showed increased mean maximum current density and a higher ‘window current’ amplitude. We demonstrate that these results are supported by an increased single channel Na+ conductance in fed neurones and, also, by a greater Nav1.2 channel density in plasma membrane‐enriched fractions of fed samples (but not in whole hippocampus preparations). These results imply fast variations on the biophysics and molecular expression of Na+ currents of rat hippocampal CA1 neurones, throughout the feeding cycle. Thus, one may expect a differentiated regulation of the intrinsic neuronal excitability, which may account for the role of the hippocampus as a processor of satiety information.

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European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. Feeding cycle alters the biophysics and molecular expression of voltage‐gated Na+ currents in rat hippocampal CA1 neurones doi:10.1111/ejn.14331 European Journal of Neuroscience 2018-12-27T12:51:21-08:00 European Journal of Neuroscience 10.1111/ejn.14331 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14331?af=R Research Report Muscle ciliary neurotrophic factor receptor α contributes to motor neuron STAT3 activation following peripheral nerve lesion Using muscle‐specific CNTFRα gene disruption and the mouse sciatic nerve crush model, this study shows muscle CNTFRα contributes to the pSTAT3 response in lesion motor neurons. Image shows pSTAT3 immunohistochemistry of spinal cord ventral horns from control (A, B) and CNTFRα‐knockdown (C, D) mice with lesioned side on right (B, D). Abstract Expression of the ciliary neurotrophic factor (CNTF) receptor essential ligand binding subunit, CNTF receptor α (CNTFRα), is induced in motor neurons and skeletal muscle following peripheral nerve lesion. We previously found muscle CNTFRα promotes motor neuron axon regeneration post‐lesion. Both nerve lesion and CNTF administration activate motor neuron signal transducer and activator of transcription 3 (STAT3), a transcription factor implicated in axon growth, suggesting CNTF receptors may contribute to the lesion‐induced STAT3 activation. However, many receptor types signal through STAT3, and if CNTF receptors contribute, motor neuron receptors seemed most likely to regulate motor neuron STAT3. To determine the role played by muscle CNTFRα, we used in vivo, muscle‐specific CNTFRα depletion in mice and report here that this selectively impairs the second phase, sustained motor neuron STAT3 activation post‐lesion. Thus, muscle CNTFRα makes an essential contribution to motor neuron STAT3 activation during axon regeneration and may thereby promote axon regeneration through such signaling. We also report CNTFRα quantitative PCR suggesting involvement of many denervated muscle types, as well as muscle damaged at the lesion site. The present data add to the evidence suggesting that enhancing muscle CNTFRα expression may promote motor neuron regeneration in trauma and disease. Nancy Lee, Rachel P. Spearry, Carolyn E. Rydyznski, A. John MacLennan https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14304?af=R European Journal of Neuroscience Muscle ciliary neurotrophic factor receptor α contributes to motor neuron STAT3 activation following peripheral nerve lesion

Using muscle‐specific CNTFRα gene disruption and the mouse sciatic nerve crush model, this study shows muscle CNTFRα contributes to the pSTAT3 response in lesion motor neurons. Image shows pSTAT3 immunohistochemistry of spinal cord ventral horns from control (A, B) and CNTFRα‐knockdown (C, D) mice with lesioned side on right (B, D).

 

Abstract

Expression of the ciliary neurotrophic factor (CNTF) receptor essential ligand binding subunit, CNTF receptor α (CNTFRα), is induced in motor neurons and skeletal muscle following peripheral nerve lesion. We previously found muscle CNTFRα promotes motor neuron axon regeneration post‐lesion. Both nerve lesion and CNTF administration activate motor neuron signal transducer and activator of transcription 3 (STAT3), a transcription factor implicated in axon growth, suggesting CNTF receptors may contribute to the lesion‐induced STAT3 activation. However, many receptor types signal through STAT3, and if CNTF receptors contribute, motor neuron receptors seemed most likely to regulate motor neuron STAT3. To determine the role played by muscle CNTFRα, we used in vivo, muscle‐specific CNTFRα depletion in mice and report here that this selectively impairs the second phase, sustained motor neuron STAT3 activation post‐lesion. Thus, muscle CNTFRα makes an essential contribution to motor neuron STAT3 activation during axon regeneration and may thereby promote axon regeneration through such signaling. We also report CNTFRα quantitative PCR suggesting involvement of many denervated muscle types, as well as muscle damaged at the lesion site. The present data add to the evidence suggesting that enhancing muscle CNTFRα expression may promote motor neuron regeneration in trauma and disease.

European Journal of Neuroscience, EarlyView. Muscle ciliary neurotrophic factor receptor α contributes to motor neuron STAT3 activation following peripheral nerve lesiondoi:10.1111/ejn.14304European Journal of Neuroscience2018-12-27T12:00:00-08:00European Journal of Neuroscience10.1111/ejn.14304 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14304?af=RSHORT COMMUNICATION Establishing online mentorship for early career researchers: Lessons from the Organization for Human Brain Mapping International Mentoring Programme Abstract Mentorship in academia facilitates personal growth through pairing trainees with mentors who can share insight and expertise. Expertise can be purely academic, on work‐life balance, personal branding and networking, or general career advice. Mentoring has been shown to be beneficial for mentees, both in terms of objective research productivity (Muschallik and Pull, 2016, Gardiner et al., 2007, Mundt, 2001, van Eck Peluchette and Jeanquart, 2000) and subjective outcomes (e.g. self‐perception as an academic, Gardiner, 2007, Ehrich et al., 2004, Mundt, 2001, van Eck Peluchette and Jeanquart, 2000). Several institutions/organizations have formal in‐person mentoring programs that pair early‐ to mid‐career researchers with mentors who are not their direct supervisors (Ehrich et al., 2004). With global integration in science, however, geographical proximity between mentors and mentees is relevant to a lesser degree. This article is protected by copyright. All rights reserved. Natalia Bielczyk, Michele Veldsman, Ayaka Ando, Chiara Caldinelli, Meena M. Makary, Aki Nikolaidis, Marzia A. Scelsi, Melanie Stefan, OHBM Student and Postdoc Special Interest Group, AmanPreet Badhwar https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14320?af=R

Abstract

Mentorship in academia facilitates personal growth through pairing trainees with mentors who can share insight and expertise. Expertise can be purely academic, on work‐life balance, personal branding and networking, or general career advice. Mentoring has been shown to be beneficial for mentees, both in terms of objective research productivity (Muschallik and Pull, 2016, Gardiner et al., 2007, Mundt, 2001, van Eck Peluchette and Jeanquart, 2000) and subjective outcomes (e.g. self‐perception as an academic, Gardiner, 2007, Ehrich et al., 2004, Mundt, 2001, van Eck Peluchette and Jeanquart, 2000). Several institutions/organizations have formal in‐person mentoring programs that pair early‐ to mid‐career researchers with mentors who are not their direct supervisors (Ehrich et al., 2004). With global integration in science, however, geographical proximity between mentors and mentees is relevant to a lesser degree.

This article is protected by copyright. All rights reserved.

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. Establishing online mentorship for early career researchers: Lessons from the Organization for Human Brain Mapping International Mentoring Programmedoi:10.1111/ejn.14320European Journal of Neuroscience2018-12-27T12:00:00-08:00European Journal of Neuroscience10.1111/ejn.14320 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14320?af=REditorial Are PARKIN patients ideal candidates for dopaminergic cell replacement therapies? Abstract Parkinson's is a heterogeneous, complex condition. Stratification of Parkinson's subtypes will be essential to identify those that will benefit most from a cell replacement therapy. Fetal mesencephalic grafts can alleviate motor symptoms in some Parkinson's patients. However, on‐going synucleinopathy results in the grafts eventually developing Lewy bodies, and they begin to fail. We propose that Parkinson's patients with PARKIN mutations may benefit most from a cell replacement therapy because (i) they often lack synucleinopathy, and (ii) their neurodegeneration is often confined to the nigrostriatal pathway. While patients with PARKIN mutations exhibit clinical signs of Parkinson's, post‐mortem studies to date indicate the majority lack Lewy bodies suggesting the nigral dopaminergic neurons are lost in a cell autonomous manner independent of α‐synuclein mechanisms. Furthermore, these patients are usually younger, slow‐progressing, and typically do not suffer from complex non‐nigral symptoms that are unlikely to be ameliorated by a cell replacement therapy. Transplantation of dopaminergic cells into the putamen of these patients will provide neurons with wild‐type PARKIN expression to re‐innervate the striatum. The focal nature of PARKIN‐mediated neurodegeneration and lack of active synucleinopathy in most young‐onset cases makes these patients ideal candidates for a dopaminergic cell replacement therapy. Strategies to improve the outcome of cell replacement therapies for sporadic Parkinson's include the use of adjunct therapeutics that target α‐synuclein spreading and the use of genetically engineered grafts that are resistant to synucleinopathy. This article is protected by copyright. All rights reserved. Tilo Kunath, Ammar Natalwala, Claire Chan, Yixi Chen, Benjamin Stecher, Martin Taylor, Sadaquate Khan, Miratul M. K. Muqit https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14314?af=R

Abstract

Parkinson's is a heterogeneous, complex condition. Stratification of Parkinson's subtypes will be essential to identify those that will benefit most from a cell replacement therapy. Fetal mesencephalic grafts can alleviate motor symptoms in some Parkinson's patients. However, on‐going synucleinopathy results in the grafts eventually developing Lewy bodies, and they begin to fail. We propose that Parkinson's patients with PARKIN mutations may benefit most from a cell replacement therapy because (i) they often lack synucleinopathy, and (ii) their neurodegeneration is often confined to the nigrostriatal pathway. While patients with PARKIN mutations exhibit clinical signs of Parkinson's, post‐mortem studies to date indicate the majority lack Lewy bodies suggesting the nigral dopaminergic neurons are lost in a cell autonomous manner independent of α‐synuclein mechanisms. Furthermore, these patients are usually younger, slow‐progressing, and typically do not suffer from complex non‐nigral symptoms that are unlikely to be ameliorated by a cell replacement therapy. Transplantation of dopaminergic cells into the putamen of these patients will provide neurons with wild‐type PARKIN expression to re‐innervate the striatum. The focal nature of PARKIN‐mediated neurodegeneration and lack of active synucleinopathy in most young‐onset cases makes these patients ideal candidates for a dopaminergic cell replacement therapy. Strategies to improve the outcome of cell replacement therapies for sporadic Parkinson's include the use of adjunct therapeutics that target α‐synuclein spreading and the use of genetically engineered grafts that are resistant to synucleinopathy.

This article is protected by copyright. All rights reserved.

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. Are PARKIN patients ideal candidates for dopaminergic cell replacement therapies?doi:10.1111/ejn.14314European Journal of Neuroscience2018-12-26T05:58:53-08:00European Journal of Neuroscience10.1111/ejn.14314 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14314?af=RSpecial Issue Article Perinatal exposure to the SSRI paroxetine alters the methylome landscape of the developing dentate gyrus Abstract Evidence in humans and rodents suggests that perinatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants can have serious long‐term consequences in offspring exposed in utero or infancy via breast milk. In spite of this, there is limited knowledge of how perinatal SSRI exposure impacts brain development and adult behavior. Children exposed to SSRIs in utero exhibit increased internalizing behavior and abnormal social behavior between the ages of 3‐6, and increased risk of depression in adolescence; however, the neurobiological changes underlying this behavior are poorly understood. In rodents, perinatal SSRI exposure perturbs hippocampal gene expression and alters adult emotional behavior (including increased depression‐like behavior). The present study demonstrates that perinatal exposure to the SSRI paroxetine disrupts leads to DNA hypomethylation and reduces DNA methyltransferase 3a (Dnmt3a) mRNA expression in the hippocampus during the second and third weeks of life. Next‐generation sequencing identified numerous differentially methylated genomic regions, including altered methylation and transcription of several dendritogenesis‐related genes. We then tested the hypothesis that transiently decreasing Dnmt3a expression in the early postnatal hippocampus would mimic the behavioral effects of perinatal SSRI exposure. We found that siRNA‐mediated knockdown of Dnmt3a in the dentate gyrus during the second to third week of life produced greater depression‐like behavior in adult female (but not male) offspring, akin to the behavioral consequences of perinatal SSRI exposure. Overall, these data suggest that perinatal SSRI exposure may increase depression‐like behaviors, at least in part, through reduced Dnmt3a expression in the developing hippocampus. This article is protected by copyright. All rights reserved. Matthew E. Glover, Chelsea R. McCoy, Elizabeth Shupe, Keaton Unroe, Nateka L. Jackson, Sarah M. Clinton https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14315?af=R

Abstract

Evidence in humans and rodents suggests that perinatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants can have serious long‐term consequences in offspring exposed in utero or infancy via breast milk. In spite of this, there is limited knowledge of how perinatal SSRI exposure impacts brain development and adult behavior. Children exposed to SSRIs in utero exhibit increased internalizing behavior and abnormal social behavior between the ages of 3‐6, and increased risk of depression in adolescence; however, the neurobiological changes underlying this behavior are poorly understood. In rodents, perinatal SSRI exposure perturbs hippocampal gene expression and alters adult emotional behavior (including increased depression‐like behavior). The present study demonstrates that perinatal exposure to the SSRI paroxetine disrupts leads to DNA hypomethylation and reduces DNA methyltransferase 3a (Dnmt3a) mRNA expression in the hippocampus during the second and third weeks of life. Next‐generation sequencing identified numerous differentially methylated genomic regions, including altered methylation and transcription of several dendritogenesis‐related genes. We then tested the hypothesis that transiently decreasing Dnmt3a expression in the early postnatal hippocampus would mimic the behavioral effects of perinatal SSRI exposure. We found that siRNA‐mediated knockdown of Dnmt3a in the dentate gyrus during the second to third week of life produced greater depression‐like behavior in adult female (but not male) offspring, akin to the behavioral consequences of perinatal SSRI exposure. Overall, these data suggest that perinatal SSRI exposure may increase depression‐like behaviors, at least in part, through reduced Dnmt3a expression in the developing hippocampus.

This article is protected by copyright. All rights reserved.

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. Perinatal exposure to the SSRI paroxetine alters the methylome landscape of the developing dentate gyrus doi:10.1111/ejn.14315 European Journal of Neuroscience 2018-12-26T05:14:38-08:00 European Journal of Neuroscience 10.1111/ejn.14315 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14315?af=R Research Report Profiles of women in science: Carmen Sandi, President of the Federation of European Neuroscience Societies Kathryn‐Mary Wakim, Dana L. Helmreich, The EJN Diversity and Inclusion Initiative https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14271?af=R European Journal of Neuroscience, EarlyView. Profiles of women in science: Carmen Sandi, President of the Federation of European Neuroscience Societies doi:10.1111/ejn.14271 European Journal of Neuroscience 2018-12-26T04:44:00-08:00 European Journal of Neuroscience 10.1111/ejn.14271 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14271?af=R EDITORIAL A Kiss to drive rhythms in reproduction In mammals, reproductive activity displays regular daily and ovarian (in female) and seasonal (in both sexes) rhythms. This review discusses how kisspeptin expressing neurons of the hypothalamus, known as potent activator of GnRH neurons, integrate daily and seasonal time cues to synchronize reproductive activity to the geophysical cycles. Abstract Reproduction, like many other biological functions, exhibits marked daily and seasonal rhythms in order to anticipate and adapt breeding activity to environmental challenges. In recent years, studies investigating the neuroendocrine mechanisms driving rhythms in reproduction have unveiled the pivotal role of hypothalamic neurons expressing kisspeptin in integrating and forwarding daily and seasonal cues to the reproductive system. The objective of this review is to summarize the knowledge on the effect and role of this neuropeptide on the mammalian hypothalamo‐pituitary‐gonadal axis and describe how it is involved in the daily control of ovulation in females and long‐term adaptation of reproduction in seasonal breeders. Valérie Simonneaux https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14287?af=R European Journal of Neuroscience A Kiss to drive rhythms in reproduction

In mammals, reproductive activity displays regular daily and ovarian (in female) and seasonal (in both sexes) rhythms. This review discusses how kisspeptin expressing neurons of the hypothalamus, known as potent activator of GnRH neurons, integrate daily and seasonal time cues to synchronize reproductive activity to the geophysical cycles.

 

Abstract

Reproduction, like many other biological functions, exhibits marked daily and seasonal rhythms in order to anticipate and adapt breeding activity to environmental challenges. In recent years, studies investigating the neuroendocrine mechanisms driving rhythms in reproduction have unveiled the pivotal role of hypothalamic neurons expressing kisspeptin in integrating and forwarding daily and seasonal cues to the reproductive system. The objective of this review is to summarize the knowledge on the effect and role of this neuropeptide on the mammalian hypothalamo‐pituitary‐gonadal axis and describe how it is involved in the daily control of ovulation in females and long‐term adaptation of reproduction in seasonal breeders.

European Journal of Neuroscience, EarlyView. A Kiss to drive rhythms in reproduction doi:10.1111/ejn.14287 European Journal of Neuroscience 2018-12-26T04:24:52-08:00 European Journal of Neuroscience 10.1111/ejn.14287 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14287?af=R SPECIAL ISSUE REVIEW Spontaneous pre‐stimulus oscillatory activity shapes the way we look: A concurrent imaging and eye‐movement study Response time is critical in determining selection control strategies. We therefore investigated how variations in timing and consequent oculomotor control are influenced by spontaneous variations in pre‐stimulus alpha oscillations. Our results show that accuracy in fast and slow responses is predicted by alpha power differences in frontal and posterior brain areas, in line with the idea that these regions may be differentially related to stimulus‐driven and goal‐driven control of selection. Abstract Previous behavioural studies have accrued evidence that response time plays a critical role in determining whether selection is influenced by stimulus saliency or target template. In the present work, we investigated to what extent the variations in timing and consequent oculomotor controls are influenced by spontaneous variations in pre‐stimulus alpha oscillations. We recorded simultaneously brain activity using magnetoencephalography (MEG) and eye movements while participants performed a visual search task. Our results show that slower saccadic reaction times were predicted by an overall stronger alpha power in the 500 ms time window preceding the stimulus onset, while weaker alpha power was a signature of faster responses. When looking separately at performance for fast and slow responses, we found evidence for two specific sources of alpha activity predicting correct versus incorrect responses. When saccades were quickly elicited, errors were predicted by stronger alpha activity in posterior areas, comprising the angular gyrus in the temporal‐parietal junction (TPJ) and possibly the lateral intraparietal area (LIP). Instead, when participants were slower in responding, an increase of alpha power in frontal eye fields (FEF), supplementary eye fields (SEF) and dorsolateral pre‐frontal cortex (DLPFC) predicted erroneous saccades. In other words, oculomotor accuracy in fast responses was predicted by alpha power differences in more posterior areas, while the accuracy in slow responses was predicted by alpha power differences in frontal areas, in line with the idea that these areas may be differentially related to stimulus‐driven and goal‐driven control of selection. Davide Paoletti, Christoph Braun, Elisabeth Julie Vargo, Wieske Zoest https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14285?af=R European Journal of Neuroscience Spontaneous pre‐stimulus oscillatory activity shapes the way we look: A concurrent imaging and eye‐movement study

Response time is critical in determining selection control strategies. We therefore investigated how variations in timing and consequent oculomotor control are influenced by spontaneous variations in pre‐stimulus alpha oscillations. Our results show that accuracy in fast and slow responses is predicted by alpha power differences in frontal and posterior brain areas, in line with the idea that these regions may be differentially related to stimulus‐driven and goal‐driven control of selection.

 

Abstract

Previous behavioural studies have accrued evidence that response time plays a critical role in determining whether selection is influenced by stimulus saliency or target template. In the present work, we investigated to what extent the variations in timing and consequent oculomotor controls are influenced by spontaneous variations in pre‐stimulus alpha oscillations. We recorded simultaneously brain activity using magnetoencephalography (MEG) and eye movements while participants performed a visual search task. Our results show that slower saccadic reaction times were predicted by an overall stronger alpha power in the 500 ms time window preceding the stimulus onset, while weaker alpha power was a signature of faster responses. When looking separately at performance for fast and slow responses, we found evidence for two specific sources of alpha activity predicting correct versus incorrect responses. When saccades were quickly elicited, errors were predicted by stronger alpha activity in posterior areas, comprising the angular gyrus in the temporal‐parietal junction (TPJ) and possibly the lateral intraparietal area (LIP). Instead, when participants were slower in responding, an increase of alpha power in frontal eye fields (FEF), supplementary eye fields (SEF) and dorsolateral pre‐frontal cortex (DLPFC) predicted erroneous saccades. In other words, oculomotor accuracy in fast responses was predicted by alpha power differences in more posterior areas, while the accuracy in slow responses was predicted by alpha power differences in frontal areas, in line with the idea that these areas may be differentially related to stimulus‐driven and goal‐driven control of selection.

European Journal of Neuroscience, EarlyView. Spontaneous pre‐stimulus oscillatory activity shapes the way we look: A concurrent imaging and eye‐movement study doi:10.1111/ejn.14285 European Journal of Neuroscience 2018-12-26T04:23:15-08:00 European Journal of Neuroscience 10.1111/ejn.14285 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14285?af=R RESEARCH REPORT Early sensitivity of evoked potentials to surface and volumetric structure during the visual perception of three‐dimensional object shape This study used event‐related potentials to reveal the higher‐order structure of three‐dimensional object shape representations in human vision. The results showed differential perceptual processing of contour, surface and volumetric shape properties during an N1 component within 140–200 ms of stimulus onset. These findings challenge theoretical models that do not attribute functional significance to surface and volumetric part structure during the visual perception of 3D object shape. Abstract This study used event‐related potentials (ERPs) to elucidate how the human visual system processes three‐dimensional (3‐D) object shape structure. In particular, we examined whether the perceptual mechanisms that support the analysis of 3‐D shape are differentially sensitive to higher order surface and volumetric part structure. Observers performed a whole‐part novel object matching task in which part stimuli comprised sub‐regions of closed edge contour, surfaces or volumetric parts. Behavioural response latency data showed an advantage in matching surfaces and volumetric parts to whole objects over contours, but no difference between surfaces and volumes. ERPs were analysed using a convergence of approaches based on stimulus dependent amplitude modulations of evoked potentials, topographic segmentation, and spatial frequency oscillations. The results showed early differential perceptual processing of contours, surfaces, and volumetric part stimuli. This was first reliably observed over occipitoparietal electrodes during the N1 (140–200 ms) with a mean peak latency of 170 ms, and continued on subsequent P2 (220–260 ms) and N2 (260–320 ms) components. The differential sensitivity in perceptual processing during the N1 was accompanied by distinct microstate patterns that distinguished among contours, surfaces and volumes, and predominant theta band activity around 4–7 Hz over right occipitoparietal and orbitofrontal sites. These results provide the first evidence of early differential perceptual processing of higher order surface and volumetric shape structure within the first 200 ms of stimulus processing. The findings challenge theoretical models of object recognition that do not attribute functional significance to surface and volumetric object structure during visual perception. E. Charles Leek, Mark V. Roberts, Neil M. Dundon, Alan J. Pegna https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14270?af=R European Journal of Neuroscience Early sensitivity of evoked potentials to surface and volumetric structure during the visual perception of three‐dimensional object shape

This study used event‐related potentials to reveal the higher‐order structure of three‐dimensional object shape representations in human vision. The results showed differential perceptual processing of contour, surface and volumetric shape properties during an N1 component within 140–200 ms of stimulus onset. These findings challenge theoretical models that do not attribute functional significance to surface and volumetric part structure during the visual perception of 3D object shape.

 

Abstract

This study used event‐related potentials (ERPs) to elucidate how the human visual system processes three‐dimensional (3‐D) object shape structure. In particular, we examined whether the perceptual mechanisms that support the analysis of 3‐D shape are differentially sensitive to higher order surface and volumetric part structure. Observers performed a whole‐part novel object matching task in which part stimuli comprised sub‐regions of closed edge contour, surfaces or volumetric parts. Behavioural response latency data showed an advantage in matching surfaces and volumetric parts to whole objects over contours, but no difference between surfaces and volumes. ERPs were analysed using a convergence of approaches based on stimulus dependent amplitude modulations of evoked potentials, topographic segmentation, and spatial frequency oscillations. The results showed early differential perceptual processing of contours, surfaces, and volumetric part stimuli. This was first reliably observed over occipitoparietal electrodes during the N1 (140–200 ms) with a mean peak latency of 170 ms, and continued on subsequent P2 (220–260 ms) and N2 (260–320 ms) components. The differential sensitivity in perceptual processing during the N1 was accompanied by distinct microstate patterns that distinguished among contours, surfaces and volumes, and predominant theta band activity around 4–7 Hz over right occipitoparietal and orbitofrontal sites. These results provide the first evidence of early differential perceptual processing of higher order surface and volumetric shape structure within the first 200 ms of stimulus processing. The findings challenge theoretical models of object recognition that do not attribute functional significance to surface and volumetric object structure during visual perception.

European Journal of Neuroscience, EarlyView. Early sensitivity of evoked potentials to surface and volumetric structure during the visual perception of three‐dimensional object shape doi:10.1111/ejn.14270 European Journal of Neuroscience 2018-12-26T04:19:20-08:00 European Journal of Neuroscience 10.1111/ejn.14270 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14270?af=R Special Issue Article Engineering synucleinopathy‐resistant human dopaminergic neurons by CRISPR‐mediated deletion of the SNCA gene CRISPR/Cas9n was used to delete the SNCA gene in human embryonic stem cells (hESCs) to generate SNCA+/− and SNCA−/− cell lines. They exhibited a similar marker profile to wild‐type dopaminergic neurons. All genotypes of neurons were treated with α‐synuclein preformed fibrils (PFFs), but only wild‐type neurons had significant Lewy‐like pathology as measured phospho‐serine‐129 α‐synuclein (pS129‐αSyn), suggesting SNCA−/− neurons would be resistant to Parkinson's disease. Abstract An emerging treatment for Parkinson's disease (PD) is cell replacement therapy. Authentic midbrain dopaminergic (mDA) neuronal precursors can be differentiated from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (iPSCs). These laboratory‐generated mDA cells have been demonstrated to mature into functional dopaminergic neurons upon transplantation into preclinical models of PD. However, clinical trials with human fetal mesenchephalic cells have shown that cell replacement grafts in PD are susceptible to Lewy body formation suggesting host‐to‐graft transfer of α‐synuclein pathology. Here, we have used CRISPR/Cas9n technology to delete the endogenous SNCA gene, encoding for α‐synuclein, in a clinical‐grade hESC line to generate SNCA+/− and SNCA−/− cell lines. These hESC lines were first differentiated into mDA neurons, and then challenged with recombinant α‐synuclein preformed fibrils (PFFs) to seed the formation for Lewy‐like pathology as measured by phosphorylation of serine‐129 of α‐synuclein (pS129‐αSyn). Wild‐type neurons were fully susceptible to the formation of protein aggregates positive for pS129‐αSyn, while SNCA+/− and SNCA−/− neurons exhibited significant resistance to the formation of this pathological mark. This work demonstrates that reducing or completely removing SNCA alleles by CRISPR/Cas9n‐mediated gene editing confers a measure of resistance to Lewy pathology. Yixi Chen, Karamjit Singh Dolt, Marco Kriek, Terry Baker, Patrick Downey, Nicola J. Drummond, Maurice A. Canham, Ammar Natalwala, Susan Rosser, Tilo Kunath https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14286?af=R European Journal of Neuroscience Engineering synucleinopathy‐resistant human dopaminergic neurons by CRISPR‐mediated deletion of the SNCA gene

CRISPR/Cas9n was used to delete the SNCA gene in human embryonic stem cells (hESCs) to generate SNCA +/− and SNCA −/− cell lines. They exhibited a similar marker profile to wild‐type dopaminergic neurons. All genotypes of neurons were treated with α‐synuclein preformed fibrils (PFFs), but only wild‐type neurons had significant Lewy‐like pathology as measured phospho‐serine‐129 α‐synuclein (pS129‐αSyn), suggesting SNCA −/− neurons would be resistant to Parkinson's disease.

 

Abstract

An emerging treatment for Parkinson's disease (PD) is cell replacement therapy. Authentic midbrain dopaminergic (mDA) neuronal precursors can be differentiated from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (iPSCs). These laboratory‐generated mDA cells have been demonstrated to mature into functional dopaminergic neurons upon transplantation into preclinical models of PD. However, clinical trials with human fetal mesenchephalic cells have shown that cell replacement grafts in PD are susceptible to Lewy body formation suggesting host‐to‐graft transfer of α‐synuclein pathology. Here, we have used CRISPR/Cas9n technology to delete the endogenous SNCA gene, encoding for α‐synuclein, in a clinical‐grade hESC line to generate SNCA +/− and SNCA −/− cell lines. These hESC lines were first differentiated into mDA neurons, and then challenged with recombinant α‐synuclein preformed fibrils (PFFs) to seed the formation for Lewy‐like pathology as measured by phosphorylation of serine‐129 of α‐synuclein (pS129‐αSyn). Wild‐type neurons were fully susceptible to the formation of protein aggregates positive for pS129‐αSyn, while SNCA +/− and SNCA −/− neurons exhibited significant resistance to the formation of this pathological mark. This work demonstrates that reducing or completely removing SNCA alleles by CRISPR/Cas9n‐mediated gene editing confers a measure of resistance to Lewy pathology.

European Journal of Neuroscience, EarlyView. Engineering synucleinopathy‐resistant human dopaminergic neurons by CRISPR‐mediated deletion of the SNCA gene doi:10.1111/ejn.14286 European Journal of Neuroscience 2018-12-21T11:23:26-08:00 European Journal of Neuroscience 10.1111/ejn.14286 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14286?af=R SPECIAL ISSUE ARTICLE Biased emotional attention in patients with dental phobia Biased motivated attention towards phobia‐relevant pictures is a typical finding in specific phobia. In contrast to previous reports, we found reduced evoked neural activation at parietal and temporal regions suggesting that dental phobia cannot be associated with the typical effects of biased motivated attention seen in other specific phobias. Instead, the general hypoactivation indicates that dental phobia shares typical characteristics with mild forms of posttraumatic stress disorder. Abstract Biased motivated attention towards phobia‐relevant pictures is a typical finding in specific phobia. In the visual system, the allocation of motivated attention is indexed by two event‐related potential components – the Early Posterior Negativity and the Late Positive Potential. Enhanced Early Posterior Negativity and Late Positive Potential amplitudes are reliably observed in specific phobia such as, for instance, snake, spider, or blood‐injection‐injury phobia and to some extent also in dental phobia. However, regarding dental phobia results are sparse and its theoretical concept is not undisputed. To further elucidate the electrophysiological characteristics of dental phobia, we investigated visual emotional processing in dental phobia patients and controls. Subjects viewed neutral, phobia‐irrelevant and phobia‐relevant pictures while magnetoencephalographic and behavioural measures were recorded. All patients reported a history of traumatic experiences and depressive and anxiety symptoms, as well as dissociative and posttraumatic symptoms. In the magnetoencephalography, patients showed generally less evoked neural activation at parietal and temporal regions and a reduced differentiation between picture categories compared to controls. At the behavioural level, patients rated phobia‐relevant pictures as clearly more negative as did controls. In contrast to previous reports, our results suggest that dental phobia cannot be associated with the typical effects of biased motivated attention seen in other specific phobias. Instead, results indicate that dental phobia shares typical characteristics with mild forms of posttraumatic stress disorder. Johanna Alexopoulos, Christian Steinberg, Nora Ellen Liebergesell‐Kilian, Berit Hoeffkes, Stephan Doering, Markus Junghöfer https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14295?af=R European Journal of Neuroscience Biased emotional attention in patients with dental phobia

Biased motivated attention towards phobia‐relevant pictures is a typical finding in specific phobia. In contrast to previous reports, we found reduced evoked neural activation at parietal and temporal regions suggesting that dental phobia cannot be associated with the typical effects of biased motivated attention seen in other specific phobias. Instead, the general hypoactivation indicates that dental phobia shares typical characteristics with mild forms of posttraumatic stress disorder.

 

Abstract

Biased motivated attention towards phobia‐relevant pictures is a typical finding in specific phobia. In the visual system, the allocation of motivated attention is indexed by two event‐related potential components – the Early Posterior Negativity and the Late Positive Potential. Enhanced Early Posterior Negativity and Late Positive Potential amplitudes are reliably observed in specific phobia such as, for instance, snake, spider, or blood‐injection‐injury phobia and to some extent also in dental phobia. However, regarding dental phobia results are sparse and its theoretical concept is not undisputed. To further elucidate the electrophysiological characteristics of dental phobia, we investigated visual emotional processing in dental phobia patients and controls. Subjects viewed neutral, phobia‐irrelevant and phobia‐relevant pictures while magnetoencephalographic and behavioural measures were recorded. All patients reported a history of traumatic experiences and depressive and anxiety symptoms, as well as dissociative and posttraumatic symptoms. In the magnetoencephalography, patients showed generally less evoked neural activation at parietal and temporal regions and a reduced differentiation between picture categories compared to controls. At the behavioural level, patients rated phobia‐relevant pictures as clearly more negative as did controls. In contrast to previous reports, our results suggest that dental phobia cannot be associated with the typical effects of biased motivated attention seen in other specific phobias. Instead, results indicate that dental phobia shares typical characteristics with mild forms of posttraumatic stress disorder.

European Journal of Neuroscience, EarlyView. Biased emotional attention in patients with dental phobiadoi:10.1111/ejn.14295European Journal of Neuroscience2018-12-21T11:13:20-08:00European Journal of Neuroscience10.1111/ejn.14295 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14295?af=RRESEARCH REPORT Neural Correlates of Cue‐ and Stress‐induced Craving in Gambling Disorders: Implications for Transcranial Magnetic Stimulation Interventions Abstract Gambling disorder (GD), currently considered a behavioral addiction, show substantial similarities with substance use disorders (SUDs) in terms of neurobiology and phenomenology. These similarities have been recognized in the DSM‐5, although several relevant differences still exist in the diagnostic criteria, in particular, with regard to the role of cue‐ and stress‐ induced craving. Craving, recently included as a new criterion for SUDs diagnosis only, is a key construct also in the pathophysiology of GD. Furthermore, brain imaging studies indicate that similar alterations in cortico‐limbic‐striatal and prefrontal control circuits underlie the emergence of craving states in both disorders. This has important implications for the identification of neurobiologically‐based anti‐craving interventions, which may be used for both GD and SUDs. In this regard, a novel neuromodulation intervention, named repetitive transcranial magnetic stimulation (rTMS), is emerging as a promising treatment for craving in SUDs, and could potentially be effective also in treating gambling urges. Here, we review the clinical neurobiological research on GD, with a specific emphasis on the neural circuits implicated in cue‐ and stress‐ craving, taking SUDs as the major comparative example. Furthermore, we describe the studies that have evaluated rTMS as a therapeutic tool for targeting and restoring the neural alterations underlying gambling urge. The manuscript concludes discussing some of the limitations of the current studies, and suggests directions for future rTMS research in GD. This article is protected by copyright. All rights reserved. Primavera A Spagnolo, Luis J Gómez Pérez, Alberto Terraneo, Luigi Gallimberti, Antonello Bonci https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14313?af=R

Abstract

Gambling disorder (GD), currently considered a behavioral addiction, show substantial similarities with substance use disorders (SUDs) in terms of neurobiology and phenomenology. These similarities have been recognized in the DSM‐5, although several relevant differences still exist in the diagnostic criteria, in particular, with regard to the role of cue‐ and stress‐ induced craving.

Craving, recently included as a new criterion for SUDs diagnosis only, is a key construct also in the pathophysiology of GD. Furthermore, brain imaging studies indicate that similar alterations in cortico‐limbic‐striatal and prefrontal control circuits underlie the emergence of craving states in both disorders. This has important implications for the identification of neurobiologically‐based anti‐craving interventions, which may be used for both GD and SUDs. In this regard, a novel neuromodulation intervention, named repetitive transcranial magnetic stimulation (rTMS), is emerging as a promising treatment for craving in SUDs, and could potentially be effective also in treating gambling urges.

Here, we review the clinical neurobiological research on GD, with a specific emphasis on the neural circuits implicated in cue‐ and stress‐ craving, taking SUDs as the major comparative example. Furthermore, we describe the studies that have evaluated rTMS as a therapeutic tool for targeting and restoring the neural alterations underlying gambling urge. The manuscript concludes discussing some of the limitations of the current studies, and suggests directions for future rTMS research in GD.

This article is protected by copyright. All rights reserved.

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. Neural Correlates of Cue‐ and Stress‐induced Craving in Gambling Disorders: Implications for Transcranial Magnetic Stimulation Interventions doi:10.1111/ejn.14313 European Journal of Neuroscience 2018-12-21T05:13:14-08:00 European Journal of Neuroscience 10.1111/ejn.14313 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14313?af=R Special Issue Review Effects of ketamine/xylazine and isoflurane on rat brain glucose metabolism measured by 18F‐fluorodeoxyglucose‐positron emission tomography Through various methods of 18F‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET) quantification, the present study found that anesthesia with ketamine‐xylazine (KX) induced a global reduction in glucose metabolism compared to isoflurane (I). The voxel‐based analyses (VBA) method revealed that animals anesthetized with KX exhibited a more marked FDG uptake pattern in the cortex and part of the limbic system relative to the mean brain uptake. The volume of distribution of FDG and its Glut1‐mediated transport across the brain membranes decreased in the KX group. Abstract The aim of the present study was to investigate changes in glucose metabolism in male Wistar rats induced by the anesthetics isoflurane and ketamine combined with xylazine via 18F‐fluorodeoxyglucose‐positron emission tomography. We analyzed the differential effects of the anesthetics on 18F‐fluorodeoxyglucose uptake and pharmacokinetics in 33 rats using quantification methods: (a) the standardized uptake value, (b) voxel‐based analyses, and (c) kinetic analysis. Both anesthetics reduced glucose uptake in the entire brain. The voxel‐based analyses detected smaller uptake reductions in the bilateral primary somatosensory system cortex and part of the limbic system in the ketamine‐xylazine (KX) group and in the vestibular nucleus in the isoflurane group. Through kinetic analysis, we found that the volume of distribution and the membrane transport rate K1 were reduced in the KX group. Through various methods of 18F‐fluorodeoxyglucose‐positron emission tomography quantification, the present study found that anesthesia with the ketamine‐xylazine combination induced a global reduction of glucose metabolism compared with isoflurane; this reduction of metabolism was relatively lower in the primary somatosensory cortex and part of the limbic system. The volume of distribution of 18F‐fluorodeoxyglucose and its Glut1‐mediated transport across the brain membranes (K1) were decreased in the KX group. Silvana Prando, Camila de Godoi Carneiro, Denise Aya Otsuki, Marcelo Tatit Sapienza https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14252?af=R European Journal of Neuroscience Effects of ketamine/xylazine and isoflurane on rat brain glucose metabolism measured by 18F‐fluorodeoxyglucose‐positron emission tomography

Through various methods of 18F‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET) quantification, the present study found that anesthesia with ketamine‐xylazine (KX) induced a global reduction in glucose metabolism compared to isoflurane (I). The voxel‐based analyses (VBA) method revealed that animals anesthetized with KX exhibited a more marked FDG uptake pattern in the cortex and part of the limbic system relative to the mean brain uptake. The volume of distribution of FDG and its Glut1‐mediated transport across the brain membranes decreased in the KX group.

 

Abstract

The aim of the present study was to investigate changes in glucose metabolism in male Wistar rats induced by the anesthetics isoflurane and ketamine combined with xylazine via 18F‐fluorodeoxyglucose‐positron emission tomography. We analyzed the differential effects of the anesthetics on 18F‐fluorodeoxyglucose uptake and pharmacokinetics in 33 rats using quantification methods: (a) the standardized uptake value, (b) voxel‐based analyses, and (c) kinetic analysis. Both anesthetics reduced glucose uptake in the entire brain. The voxel‐based analyses detected smaller uptake reductions in the bilateral primary somatosensory system cortex and part of the limbic system in the ketamine‐xylazine (KX) group and in the vestibular nucleus in the isoflurane group. Through kinetic analysis, we found that the volume of distribution and the membrane transport rate K1 were reduced in the KX group. Through various methods of 18F‐fluorodeoxyglucose‐positron emission tomography quantification, the present study found that anesthesia with the ketamine‐xylazine combination induced a global reduction of glucose metabolism compared with isoflurane; this reduction of metabolism was relatively lower in the primary somatosensory cortex and part of the limbic system. The volume of distribution of 18F‐fluorodeoxyglucose and its Glut1‐mediated transport across the brain membranes (K1) were decreased in the KX group.

European Journal of Neuroscience, EarlyView. Effects of ketamine/xylazine and isoflurane on rat brain glucose metabolism measured by 18F‐fluorodeoxyglucose‐positron emission tomographydoi:10.1111/ejn.14252European Journal of Neuroscience2018-12-21T03:49:36-08:00European Journal of Neuroscience10.1111/ejn.14252 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14252?af=RRESEARCH REPORT Neurofeedback: principles, appraisal and outstanding issues Abstract Neurofeedback is a form of brain training in which subjects are fed back information about some measure of their brain activity which they are instructed to modify in a way thought to be functionally advantageous. Over the last twenty years, neurofeedback has been used to treat various neurological and psychiatric conditions, and to improve cognitive function in various contexts. However, in spite of a growing popularity, neurofeedback protocols typically make (often covert) assumptions on what aspects of brain activity to target, where in the brain to act and how, which have far‐reaching implications for the assessment of its potential and efficacy. Here we critically examine some conceptual and methodological issues associated with the way neurofeedback's general objectives and neural targets are defined. The neural mechanisms through which neurofeedback may act at various spatial and temporal scales, and the way its efficacy is appraised are reviewed, and the extent to which neurofeedback may be used to control functional brain activity discussed. Finally, it is proposed that gauging neurofeedback's potential, as well as assessing and improving its efficacy will require better understanding of various fundamental aspects of brain dynamics and a more precise definition of functional brain activity and brain‐behaviour relationships. This article is protected by copyright. All rights reserved. David Papo https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14312?af=R

Abstract

Neurofeedback is a form of brain training in which subjects are fed back information about some measure of their brain activity which they are instructed to modify in a way thought to be functionally advantageous. Over the last twenty years, neurofeedback has been used to treat various neurological and psychiatric conditions, and to improve cognitive function in various contexts. However, in spite of a growing popularity, neurofeedback protocols typically make (often covert) assumptions on what aspects of brain activity to target, where in the brain to act and how, which have far‐reaching implications for the assessment of its potential and efficacy. Here we critically examine some conceptual and methodological issues associated with the way neurofeedback's general objectives and neural targets are defined. The neural mechanisms through which neurofeedback may act at various spatial and temporal scales, and the way its efficacy is appraised are reviewed, and the extent to which neurofeedback may be used to control functional brain activity discussed. Finally, it is proposed that gauging neurofeedback's potential, as well as assessing and improving its efficacy will require better understanding of various fundamental aspects of brain dynamics and a more precise definition of functional brain activity and brain‐behaviour relationships.

This article is protected by copyright. All rights reserved.

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. Neurofeedback: principles, appraisal and outstanding issuesdoi:10.1111/ejn.14312European Journal of Neuroscience2018-12-20T02:18:00-08:00European Journal of Neuroscience10.1111/ejn.14312 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14312?af=RReview Article Kalirin‐7 prevents dendritic spine dysgenesis induced by amyloid beta‐derived oligomers Abstract Synapse degeneration and dendritic spine dysgenesis are believed to be crucial early steps in Alzheimer's disease (AD), and correlate with cognitive deficits in AD patients. Soluble amyloid beta (Aβ)‐derived oligomers, also termed Aβ‐derived diffusible ligands (ADDLs), accumulate in the brain of AD patients and play a crucial role in AD pathogenesis. ADDLs bind to mature hippocampal neurons, induce structural changes in dendritic spines and contribute to neuronal death. However, mechanisms underlying structural and toxic effects are not fully understood. Here we report that ADDLs bind to cultured mature cortical pyramidal neurons and induce spine dysgenesis. ADDL treatment induced the rapid depletion of kalirin‐7, a brain‐specific guanine‐nucleotide exchange factor for the small GTPase Rac1, from spines. Kalirin‐7 is key regulator of dendritic spine morphogenesis and maintenance in forebrain pyramidal neurons and here we show that overexpression of kalirin‐7 prevents ADDL‐induced spine degeneration. Taken together, our results suggest that kalirin‐7 may play a role in the early events leading to synapse degeneration, and its pharmacological activation may prevent or delay synapse pathology in AD. This article is protected by copyright. All rights reserved. Zhong Xie, Lauren P. Shapiro, Michael E. Cahill, Theron A. Russell, Pascale N. Lacor, William L. Klein, Peter Penzes https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14311?af=R

Abstract

Synapse degeneration and dendritic spine dysgenesis are believed to be crucial early steps in Alzheimer's disease (AD), and correlate with cognitive deficits in AD patients. Soluble amyloid beta (Aβ)‐derived oligomers, also termed Aβ‐derived diffusible ligands (ADDLs), accumulate in the brain of AD patients and play a crucial role in AD pathogenesis. ADDLs bind to mature hippocampal neurons, induce structural changes in dendritic spines and contribute to neuronal death. However, mechanisms underlying structural and toxic effects are not fully understood. Here we report that ADDLs bind to cultured mature cortical pyramidal neurons and induce spine dysgenesis. ADDL treatment induced the rapid depletion of kalirin‐7, a brain‐specific guanine‐nucleotide exchange factor for the small GTPase Rac1, from spines. Kalirin‐7 is key regulator of dendritic spine morphogenesis and maintenance in forebrain pyramidal neurons and here we show that overexpression of kalirin‐7 prevents ADDL‐induced spine degeneration. Taken together, our results suggest that kalirin‐7 may play a role in the early events leading to synapse degeneration, and its pharmacological activation may prevent or delay synapse pathology in AD.

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European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. Kalirin‐7 prevents dendritic spine dysgenesis induced by amyloid beta‐derived oligomers doi:10.1111/ejn.14311 European Journal of Neuroscience 2018-12-19T04:03:03-08:00 European Journal of Neuroscience 10.1111/ejn.14311 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14311?af=R Short Communication Reduced late mismatch negativity and auditory sustained potential to rule‐based patterns in schizophrenia We investigated complex rule‐based novelty detection in individuals with chronic schizophrenia by measuring mismatch negativity (MMN) and the auditory sustained potential (ASP) to deviant tones in a complex zig‐zag pitch pattern that cannot be predicted by simple linear rules. Both the ASP and late MMN were significantly reduced in schizophrenia compared to controls, suggesting deficits later in the auditory hierarchy responsible for auditory segmentation and deviance detection abilities. Abstract Complex rule‐based auditory processing is abnormal in individuals with long‐term schizophrenia (SZ), as demonstrated by reduced mismatch negativity (MMN) to deviants in rule‐based patterns and reduced auditory sustained potential (ASP) that appears when grouping tones together. Together, this suggests deficits later in the auditory processing hierarchy in Sz. Here, MMN and ASP were elicited by deviations from a complex zig‐zag pitch pattern that cannot be predicted by simple linear rules. Twenty‐seven SZ and 26 matched healthy controls (HC) participated. Frequent groups of patterns contained eight tones that zig‐zagged in a two‐up one‐down pitch‐based paradigm. There were two deviant patterns: the final tone was either higher in pitch than expected (creating a jump in pitch) or was repeated. Simple MMN to pitch‐deviants among repetitive tones was measured for comparison. Sz exhibited a smaller pitch MMN compared to HC as expected. HC produced a late MMN in response to the repeat and jump‐deviant and a larger ASP to the standard group of tones, all of which were significantly blunted in SZ. In Sz, the amplitude of the late complex MMN was related to neuropsychological functioning, whereas ASP was not. ASP and late MMN did not significantly correlate in HC or in Sz, suggesting that they are not dependent on one another and may originate within distinct processing streams. Together, this suggests multiple deficits later in the auditory sensory‐perceptual hierarchy in Sz, with impairments evident in both segmentation and deviance detection abilities. Sarah M. Haigh, Brian A. Coffman, Timothy K. Murphy, Christiana D. Butera, Justin R. Leiter‐McBeth, Dean F. Salisbury https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14274?af=R European Journal of Neuroscience Reduced late mismatch negativity and auditory sustained potential to rule‐based patterns in schizophrenia

We investigated complex rule‐based novelty detection in individuals with chronic schizophrenia by measuring mismatch negativity (MMN) and the auditory sustained potential (ASP) to deviant tones in a complex zig‐zag pitch pattern that cannot be predicted by simple linear rules. Both the ASP and late MMN were significantly reduced in schizophrenia compared to controls, suggesting deficits later in the auditory hierarchy responsible for auditory segmentation and deviance detection abilities.

 

Abstract

Complex rule‐based auditory processing is abnormal in individuals with long‐term schizophrenia (SZ), as demonstrated by reduced mismatch negativity (MMN) to deviants in rule‐based patterns and reduced auditory sustained potential (ASP) that appears when grouping tones together. Together, this suggests deficits later in the auditory processing hierarchy in Sz. Here, MMN and ASP were elicited by deviations from a complex zig‐zag pitch pattern that cannot be predicted by simple linear rules. Twenty‐seven SZ and 26 matched healthy controls (HC) participated. Frequent groups of patterns contained eight tones that zig‐zagged in a two‐up one‐down pitch‐based paradigm. There were two deviant patterns: the final tone was either higher in pitch than expected (creating a jump in pitch) or was repeated. Simple MMN to pitch‐deviants among repetitive tones was measured for comparison. Sz exhibited a smaller pitch MMN compared to HC as expected. HC produced a late MMN in response to the repeat and jump‐deviant and a larger ASP to the standard group of tones, all of which were significantly blunted in SZ. In Sz, the amplitude of the late complex MMN was related to neuropsychological functioning, whereas ASP was not. ASP and late MMN did not significantly correlate in HC or in Sz, suggesting that they are not dependent on one another and may originate within distinct processing streams. Together, this suggests multiple deficits later in the auditory sensory‐perceptual hierarchy in Sz, with impairments evident in both segmentation and deviance detection abilities.

European Journal of Neuroscience, EarlyView. Reduced late mismatch negativity and auditory sustained potential to rule‐based patterns in schizophreniadoi:10.1111/ejn.14274European Journal of Neuroscience2018-12-18T04:58:28-08:00European Journal of Neuroscience10.1111/ejn.14274 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14274?af=RRESEARCH REPORT Insular Resting State Functional Connectivity is Associated with Gut Microbiota Diversity Abstract The gut microbiota has recently gained attention as a possible modulator of brain activity. A number of reports suggest that the microbiota may be associated with neuropsychiatric conditions such as major depressive disorder, autism, and anxiety. The gut microbiota is thought to influence the brain via vagus nerve signaling, among other possible mechanisms. The insula processes and integrates these vagal signals. To determine if microbiota diversity and structure modulate brain activity, we collected fecal samples and examined insular function using resting state functional connectivity (RSFC). Thirty healthy participants (non‐smokers, tobacco smokers, and electronic cigarette users, n=10 each) were studied. We found that the RSFC between the insula and several regions (frontal pole left, lateral occipital cortex right, lingual gyrus right, and cerebellum 4, 5 and vermis 9) were associated with bacterial microbiota diversity and structure. In addition, two specific bacteria genera, Prevotella and Bacteroides, were specifically different in tobacco smokers and also associated with insular connectivity. In conclusion, we show that insular connectivity is associated with microbiome diversity, structure, and at least two specific bateria genera. Furthemore, this association is potentially modulated by tobacco smoking, although the sample sizes for the different smoking groups were small and this result needs validation in a larger cohort. While replication is necessary, the microbiota is a readily accesible therapeutic target for modulating insular connectivity, which has previously been shown to be abnormal in anxiety and tobacco use disorders. This article is protected by copyright. All rights reserved. Kaylah Curtis, Christopher J. Stewart, Meghan Robinson, David L Molfese, Savannah N Gosnell, Thomas R Kosten, Joseph F Petrosino, Richard De La Garza, Ramiro Salas https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14305?af=R

Abstract

The gut microbiota has recently gained attention as a possible modulator of brain activity. A number of reports suggest that the microbiota may be associated with neuropsychiatric conditions such as major depressive disorder, autism, and anxiety. The gut microbiota is thought to influence the brain via vagus nerve signaling, among other possible mechanisms. The insula processes and integrates these vagal signals. To determine if microbiota diversity and structure modulate brain activity, we collected fecal samples and examined insular function using resting state functional connectivity (RSFC). Thirty healthy participants (non‐smokers, tobacco smokers, and electronic cigarette users, n=10 each) were studied. We found that the RSFC between the insula and several regions (frontal pole left, lateral occipital cortex right, lingual gyrus right, and cerebellum 4, 5 and vermis 9) were associated with bacterial microbiota diversity and structure. In addition, two specific bacteria genera, Prevotella and Bacteroides, were specifically different in tobacco smokers and also associated with insular connectivity. In conclusion, we show that insular connectivity is associated with microbiome diversity, structure, and at least two specific bateria genera. Furthemore, this association is potentially modulated by tobacco smoking, although the sample sizes for the different smoking groups were small and this result needs validation in a larger cohort. While replication is necessary, the microbiota is a readily accesible therapeutic target for modulating insular connectivity, which has previously been shown to be abnormal in anxiety and tobacco use disorders.

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European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. Insular Resting State Functional Connectivity is Associated with Gut Microbiota Diversitydoi:10.1111/ejn.14305European Journal of Neuroscience2018-12-16T02:49:14-08:00European Journal of Neuroscience10.1111/ejn.14305 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14305?af=RSpecial Issue Article Repetition Priming Effects for Famous Faces through Dynamic Causal Modelling of Latency‐Corrected Event‐Related Brain Potentials Abstract Repetition priming, that is, the repeated processing of a stimulus, facilitates performance. However, the neural underpinnings of repetition priming for famous faces in terms of effective connectivity is not known. Here we investigated this problem using dynamic causal modelling of latency‐corrected event‐related brain potentials (RERPs). Source waveforms of RERP‐derived sources in the Occipital Lobe, Fusiform Gyrus, Mediotemporal Lobe, Prefrontal Cortex and Anterotemporal Lobe of each hemisphere entered into models with only forward (F) or also backward (FB) connections. Based on the framework of predictive coding formulated for repetition suppression, modulations of F and FB connections were expected for sources that displayed priming effects in their source waveforms. Hence, neural sources in each hemisphere were fitted with either F or FB connections. Inter‐hemispheric connections were considered between homologous areas and were allowed to be modulated in an incremental manner resulting in a model‐space that comprised of 24 models. Bayesian model averaging across models revealed effective bidirectional connectivity between the Fusiform Gyrus (face perception) and Prefrontal Cortex (decision making) in both hemispheres to be modulated by priming. In the left hemisphere, there is also a substantial involvement from the Mediotemporal Lobe, indicating the facilitation of automatic retrieval of the famous person's names. Furthermore, there is evidence that the priming is supported by connections from the right to the left Fusiform Gyri possibly in the service of inter‐hemispheric cooperation. Altogether, the study indicates that along with top‐down modulations, efficient processing within and across the two hemispheres is crucial for famous face priming. This article is protected by copyright. All rights reserved. Rajan Kashyap, Sagarika Bhattacharjee, Werner Sommer, Changsong Zhou https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14303?af=R

Abstract

Repetition priming, that is, the repeated processing of a stimulus, facilitates performance. However, the neural underpinnings of repetition priming for famous faces in terms of effective connectivity is not known. Here we investigated this problem using dynamic causal modelling of latency‐corrected event‐related brain potentials (RERPs). Source waveforms of RERP‐derived sources in the Occipital Lobe, Fusiform Gyrus, Mediotemporal Lobe, Prefrontal Cortex and Anterotemporal Lobe of each hemisphere entered into models with only forward (F) or also backward (FB) connections. Based on the framework of predictive coding formulated for repetition suppression, modulations of F and FB connections were expected for sources that displayed priming effects in their source waveforms. Hence, neural sources in each hemisphere were fitted with either F or FB connections. Inter‐hemispheric connections were considered between homologous areas and were allowed to be modulated in an incremental manner resulting in a model‐space that comprised of 24 models. Bayesian model averaging across models revealed effective bidirectional connectivity between the Fusiform Gyrus (face perception) and Prefrontal Cortex (decision making) in both hemispheres to be modulated by priming. In the left hemisphere, there is also a substantial involvement from the Mediotemporal Lobe, indicating the facilitation of automatic retrieval of the famous person's names. Furthermore, there is evidence that the priming is supported by connections from the right to the left Fusiform Gyri possibly in the service of inter‐hemispheric cooperation. Altogether, the study indicates that along with top‐down modulations, efficient processing within and across the two hemispheres is crucial for famous face priming.

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European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. Repetition Priming Effects for Famous Faces through Dynamic Causal Modelling of Latency‐Corrected Event‐Related Brain Potentialsdoi:10.1111/ejn.14303European Journal of Neuroscience2018-12-14T05:19:48-08:00European Journal of Neuroscience10.1111/ejn.14303 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14303?af=RResearch Report Acid Sensing Ion Channel 2: a new potential player in the pathophysiology of multiple sclerosis Abstract Acid Sensing Ion Channel (ASICs) are proton‐gated channels involved in multiple biological functions such as: pain modulation, mechanosensation, neurotransmission and neurodegeneration. Earlier, we described the genetic association, within the Nuoro population, between multiple sclerosis (MS) and rs28936, located in ASIC2 3’UTR. Here we investigated the potential involvement of ASIC2 in MS inflammatory process. We induced experimental autoimmune encephalomyelitis (EAE) in wild‐type (WT), knockout Asic1‐/‐ and Asic2‐/‐ mice and observed a significant reduction of clinical score in Asic1‐/‐ mice and a significant reduction of the clinical score in Asic2‐/‐ mice in a limited time window (i.e at days 20‐23 after immunization). Immunohistochemistry confirmed the reduction of adaptive immune cell infiltrates in the spinal cord of EAE Asic1‐/‐ mice. Analysis of mechanical allodynia, showed a significant higher pain threshold in Asic2‐/‐ mice under physiological conditions, before immunization, as compared to WT mice and Asic1‐/‐. A significant reduction in pain threshold was observed in all 3 strains of mice after immunization. More importantly, analysis of human autoptic brain tissue in MS and control samples showed an increase of ASIC2 mRNA in MS samples. Subsequently, in vitro luciferase reporter gene assays, showed that ASIC2 expression is under possible miRNA regulation, in a rs28936 allele‐specific manner. Taken together, these findings suggest a potential role of ASIC2 in the pathophysiology of MS. This article is protected by copyright. All rights reserved. Teresa Fazia, Roberta Pastorino, Serena Notartomaso, Carla Busceti, Tiziana Imbriglio, Milena Cannella, Davide Gentilini, Gabriele Morani, Anna Ticca, Pierpaolo Bitti, Carlo Berzuini, Tamas Dalmay, Giuseppe Battaglia, Luisa Bernardinelli https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14302?af=R

Abstract

Acid Sensing Ion Channel (ASICs) are proton‐gated channels involved in multiple biological functions such as: pain modulation, mechanosensation, neurotransmission and neurodegeneration. Earlier, we described the genetic association, within the Nuoro population, between multiple sclerosis (MS) and rs28936, located in ASIC2 3’UTR. Here we investigated the potential involvement of ASIC2 in MS inflammatory process. We induced experimental autoimmune encephalomyelitis (EAE) in wild‐type (WT), knockout Asic1‐/‐ and Asic2‐/‐ mice and observed a significant reduction of clinical score in Asic1‐/‐ mice and a significant reduction of the clinical score in Asic2‐/‐ mice in a limited time window (i.e at days 20‐23 after immunization). Immunohistochemistry confirmed the reduction of adaptive immune cell infiltrates in the spinal cord of EAE Asic1‐/‐ mice. Analysis of mechanical allodynia, showed a significant higher pain threshold in Asic2‐/‐ mice under physiological conditions, before immunization, as compared to WT mice and Asic1‐/‐. A significant reduction in pain threshold was observed in all 3 strains of mice after immunization. More importantly, analysis of human autoptic brain tissue in MS and control samples showed an increase of ASIC2 mRNA in MS samples. Subsequently, in vitro luciferase reporter gene assays, showed that ASIC2 expression is under possible miRNA regulation, in a rs28936 allele‐specific manner. Taken together, these findings suggest a potential role of ASIC2 in the pathophysiology of MS.

This article is protected by copyright. All rights reserved.

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. Acid Sensing Ion Channel 2: a new potential player in the pathophysiology of multiple sclerosis doi:10.1111/ejn.14302 European Journal of Neuroscience 2018-12-14T04:38:55-08:00 European Journal of Neuroscience 10.1111/ejn.14302 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14302?af=R Research Report Circadian pacemaker neurons of the Madeira cockroach are inhibited and activated by GABAA and GABAB receptors Combining Ca2+ imaging of primary cell cultures of the cockroach circadian clock with pharmacology showed that GABA‐dependent decreases in calcium baseline levels could be accounted for by different combinations of inhibitory/excitatory GABAA or GABAB receptors. In contrast, excitatory actions of GABA required excitatory GABAB receptors, combined with excitatory or inhibitory GABAA receptors. This is the first report of excitatory GABAB receptors in circadian clock cells. Abstract GABA is the most abundant neurotransmitter in the circadian pacemaker circuits of mammals and insects. In the Madeira cockroach the accessory medulla (AME) in the brain′s optic lobes is the circadian clock that orchestrates rest‐activity rhythms in synchrony with light dark cycles. Three prominent GABAergic tracts connect the AME to termination sites of compound eye photoreceptors in the lamina and medulla. Parallel GABAergic light entrainment pathways were suggested to either advance or delay the clock for adjustment to changing photoperiods. In agreement with this hypothesis GABA activated or inhibited AME clock neurons, allowing for the distinction of three different GABA response types. Here, we examined which GABA receptors are responsible for these response types. We found that both ionotropic GABAA receptors and metabotropic GABAB receptors were expressed in AME clock cells. Via different signalling pathways, either one of them could account for all three GABA response types. The muscimol‐dependently activated GABAA receptor formed a chloride channel, while the SKF 97541‐dependently activated GABAB receptor signalled via G‐proteins, apparently targeting potassium channels. Expression of chloride exporters or importers determined whether GABAA receptor activation hyper‐ or depolarized AME neurons. For GABAB receptor responses second messenger gated channels present in the clock cells appeared to decide about the polarity of the GABA response. In summary, circadian clock neurons co‐expressed inhibitory and/or excitatory GABAA and GABAB receptors in various combinations, while cotransporter expression and the set of second messenger gated ion channels present allowed for distinct signalling in different clock neurons. Maria Giese, HongYing Wei, Monika Stengl https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14268?af=R European Journal of Neuroscience Circadian pacemaker neurons of the Madeira cockroach are inhibited and activated by GABAA and GABAB receptors

Combining Ca2+ imaging of primary cell cultures of the cockroach circadian clock with pharmacology showed that GABA‐dependent decreases in calcium baseline levels could be accounted for by different combinations of inhibitory/excitatory GABAA or GABAB receptors. In contrast, excitatory actions of GABA required excitatory GABAB receptors, combined with excitatory or inhibitory GABAA receptors. This is the first report of excitatory GABAB receptors in circadian clock cells.

 

Abstract

GABA is the most abundant neurotransmitter in the circadian pacemaker circuits of mammals and insects. In the Madeira cockroach the accessory medulla (AME) in the brain′s optic lobes is the circadian clock that orchestrates rest‐activity rhythms in synchrony with light dark cycles. Three prominent GABAergic tracts connect the AME to termination sites of compound eye photoreceptors in the lamina and medulla. Parallel GABAergic light entrainment pathways were suggested to either advance or delay the clock for adjustment to changing photoperiods. In agreement with this hypothesis GABA activated or inhibited AME clock neurons, allowing for the distinction of three different GABA response types. Here, we examined which GABA receptors are responsible for these response types. We found that both ionotropic GABAA receptors and metabotropic GABAB receptors were expressed in AME clock cells. Via different signalling pathways, either one of them could account for all three GABA response types. The muscimol‐dependently activated GABAA receptor formed a chloride channel, while the SKF 97541‐dependently activated GABAB receptor signalled via G‐proteins, apparently targeting potassium channels. Expression of chloride exporters or importers determined whether GABAA receptor activation hyper‐ or depolarized AME neurons. For GABAB receptor responses second messenger gated channels present in the clock cells appeared to decide about the polarity of the GABA response. In summary, circadian clock neurons co‐expressed inhibitory and/or excitatory GABAA and GABAB receptors in various combinations, while cotransporter expression and the set of second messenger gated ion channels present allowed for distinct signalling in different clock neurons.

European Journal of Neuroscience, EarlyView. Circadian pacemaker neurons of the Madeira cockroach are inhibited and activated by GABAA and GABAB receptors doi:10.1111/ejn.14268 European Journal of Neuroscience 2018-12-14T03:28:58-08:00 European Journal of Neuroscience 10.1111/ejn.14268 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14268?af=R SPECIAL ISSUE ARTICLE Behavioral, neuroendocrine and physiological indicators of the circadian biology of male and female rabbits The circadian biology of rabbits is discussed and illustrated within three areas: (A) The “classic” circadian system, regulated by light, mediated by the suprachiasmatic nucleus (SCN), and modulated by a food‐entrained oscillator (FEO); (B) Suckling stimulation is a non‐photic zeitgeber interacting with the circadian system to regulate the display of the single daily nursing bout characteristic of mother rabbits; (C) Sleep and the immune system are modulated by the circadian system and also by each other, thus determining the response to infection and recovery from it. Abstract Adult rabbits show robust circadian rhythms of: nursing, food and water intake, hard faeces excretion, locomotion, body temperature, blood and intraocular pressure, corticosteroid secretion, and sleep. Control of several circadian rhythms involves a light‐entrained circadian clock and a food‐entrained oscillator. Nursing periodicity, however, relies on a suckling stimulation threshold. Brain structures regulating this activity include the paraventricular nucleus and preoptic area, as determined by lesions and quantification of cFOS‐ and PER1 clock gene‐immunoreactive proteins. Melatonin synthesis in the rabbit pineal gland shows a diurnal rhythm, with highest values at night and lowest ones during the day. In kits the main zeitgeber is milk intake, which synchronizes locomotor activity, body temperature, and corticosterone secretion. Brain regions involved in these effects include the median preoptic nucleus and several olfactory structures. As models for particular human illnesses rabbits have been valuable for studying glaucoma and cardiovascular disease. Circadian variations in intraocular pressure (main risk factor for glaucoma) have been found, with highest values at night, which depend on sympathetic innervation. Rabbits fed a high fat diet develop cholesterol plaques and high blood pressure, as do humans, and such increased fat intake directly modulates cardiovascular homeostasis and circadian patterns, independently of white adipose tissue accumulation. Rabbits have also been useful to investigate the characteristics of sleep across the day and its modulation by infections, cytokines and other endogenous humoral factors. Rabbit circadian biology warrants deeper investigation of the role of the suprachiasmatic nucleus in regulating most behavioral and physiological rhythms described above. Raúl Aguilar‐Roblero, Gabriela González‐Mariscal https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14265?af=R European Journal of Neuroscience Behavioral, neuroendocrine and physiological indicators of the circadian biology of male and female rabbits

The circadian biology of rabbits is discussed and illustrated within three areas: (A) The “classic” circadian system, regulated by light, mediated by the suprachiasmatic nucleus (SCN), and modulated by a food‐entrained oscillator (FEO); (B) Suckling stimulation is a non‐photic zeitgeber interacting with the circadian system to regulate the display of the single daily nursing bout characteristic of mother rabbits; (C) Sleep and the immune system are modulated by the circadian system and also by each other, thus determining the response to infection and recovery from it.

 

Abstract

Adult rabbits show robust circadian rhythms of: nursing, food and water intake, hard faeces excretion, locomotion, body temperature, blood and intraocular pressure, corticosteroid secretion, and sleep. Control of several circadian rhythms involves a light‐entrained circadian clock and a food‐entrained oscillator. Nursing periodicity, however, relies on a suckling stimulation threshold. Brain structures regulating this activity include the paraventricular nucleus and preoptic area, as determined by lesions and quantification of cFOS‐ and PER1 clock gene‐immunoreactive proteins. Melatonin synthesis in the rabbit pineal gland shows a diurnal rhythm, with highest values at night and lowest ones during the day. In kits the main zeitgeber is milk intake, which synchronizes locomotor activity, body temperature, and corticosterone secretion. Brain regions involved in these effects include the median preoptic nucleus and several olfactory structures. As models for particular human illnesses rabbits have been valuable for studying glaucoma and cardiovascular disease. Circadian variations in intraocular pressure (main risk factor for glaucoma) have been found, with highest values at night, which depend on sympathetic innervation. Rabbits fed a high fat diet develop cholesterol plaques and high blood pressure, as do humans, and such increased fat intake directly modulates cardiovascular homeostasis and circadian patterns, independently of white adipose tissue accumulation. Rabbits have also been useful to investigate the characteristics of sleep across the day and its modulation by infections, cytokines and other endogenous humoral factors. Rabbit circadian biology warrants deeper investigation of the role of the suprachiasmatic nucleus in regulating most behavioral and physiological rhythms described above.

European Journal of Neuroscience, EarlyView. Behavioral, neuroendocrine and physiological indicators of the circadian biology of male and female rabbits doi:10.1111/ejn.14265 European Journal of Neuroscience 2018-12-14T03:28:57-08:00 European Journal of Neuroscience 10.1111/ejn.14265 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14265?af=R SPECIAL ISSUE REVIEW Repeated blast model of mild traumatic brain injury alters oxycodone self‐administration and drug seeking Rats were exposed to repeated blast mild traumatic brain injury, then underwent oxycodone self‐administration and seeking. Injured rats self‐administered less oxycodone under an FR‐2 schedule but were no different under an FR‐4 schedule. Despite lower intake, injured rats had significantly greater responding during extinction, and the relationship between prior drug intake and drug seeking observed in sham‐injured animals was lost in injured rats. Abstract Each year, traumatic brain injuries (TBI) affect millions worldwide. Mild TBIs (mTBI) are the most prevalent and can lead to a range of neurobehavioral problems, including substance abuse. A single blast exposure, inducing mTBI alters the medial prefrontal cortex, an area implicated in addiction, for at least 30 days post injury in rats. Repeated blast exposures result in greater physiological and behavioral dysfunction than single exposure; however, the impact of repeated mTBI on addiction is unknown. In this study, the effect of mTBI on various stages of oxycodone use was examined. Male Sprague Dawley rats were exposed to a blast model of mTBI once per day for 3 days. Rats were trained to self‐administer oxycodone during short (2 h) and long (6 h) access sessions. Following abstinence, rats underwent extinction and two cued reinstatement sessions. Sham and rbTBI rats had similar oxycodone intake, extinction responding and cued reinstatement of drug seeking. A second group of rats were trained to self‐administer oxycodone with varying reinforcement schedules (fixed ratio (FR)‐2 and FR‐4). Under an FR‐2 schedule, rbTBI‐exposed rats earned fewer reinforcers than sham‐exposed rats. During 10 extinction sessions, the rbTBI‐exposed rats exhibited significantly more seeking for oxycodone than the sham‐injured rats. There was a positive correlation between total oxycodone intake and day 1 extinction drug seeking in sham, but not in rbTBI‐exposed rats. Together, this suggests that rbTBI‐exposed rats are more sensitive to oxycodone‐associated cues during reinstatement than sham‐exposed rats and that rbTBI may disrupt the relationship between oxycodone intake and seeking. Natalie N. Nawarawong, Megan Slaker, Matt Muelbl, Alok S. Shah, Rachel Chiariello, Lindsay D. Nelson, Matthew D. Budde, Brian D. Stemper, Christopher M. Olsen https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14281?af=R European Journal of Neuroscience Repeated blast model of mild traumatic brain injury alters oxycodone self‐administration and drug seeking

Rats were exposed to repeated blast mild traumatic brain injury, then underwent oxycodone self‐administration and seeking. Injured rats self‐administered less oxycodone under an FR‐2 schedule but were no different under an FR‐4 schedule. Despite lower intake, injured rats had significantly greater responding during extinction, and the relationship between prior drug intake and drug seeking observed in sham‐injured animals was lost in injured rats.

 

Abstract

Each year, traumatic brain injuries (TBI) affect millions worldwide. Mild TBIs (mTBI) are the most prevalent and can lead to a range of neurobehavioral problems, including substance abuse. A single blast exposure, inducing mTBI alters the medial prefrontal cortex, an area implicated in addiction, for at least 30 days post injury in rats. Repeated blast exposures result in greater physiological and behavioral dysfunction than single exposure; however, the impact of repeated mTBI on addiction is unknown. In this study, the effect of mTBI on various stages of oxycodone use was examined. Male Sprague Dawley rats were exposed to a blast model of mTBI once per day for 3 days. Rats were trained to self‐administer oxycodone during short (2 h) and long (6 h) access sessions. Following abstinence, rats underwent extinction and two cued reinstatement sessions. Sham and rbTBI rats had similar oxycodone intake, extinction responding and cued reinstatement of drug seeking. A second group of rats were trained to self‐administer oxycodone with varying reinforcement schedules (fixed ratio (FR)‐2 and FR‐4). Under an FR‐2 schedule, rbTBI‐exposed rats earned fewer reinforcers than sham‐exposed rats. During 10 extinction sessions, the rbTBI‐exposed rats exhibited significantly more seeking for oxycodone than the sham‐injured rats. There was a positive correlation between total oxycodone intake and day 1 extinction drug seeking in sham, but not in rbTBI‐exposed rats. Together, this suggests that rbTBI‐exposed rats are more sensitive to oxycodone‐associated cues during reinstatement than sham‐exposed rats and that rbTBI may disrupt the relationship between oxycodone intake and seeking.

European Journal of Neuroscience, EarlyView. Repeated blast model of mild traumatic brain injury alters oxycodone self‐administration and drug seeking doi:10.1111/ejn.14281 European Journal of Neuroscience 2018-12-14T03:10:13-08:00 European Journal of Neuroscience 10.1111/ejn.14281 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14281?af=R Special Issue Article Architecture and organization of mouse posterior parietal cortex relative to extrastriate areas The posterior parietal cortex (PPC) is a multifaceted region of cortex supporting several cognitive functions. Recent years have seen an increase in the use of rodents to study PPC, but a coherent definition of PPC in mice is still lacking. We addressed this by characterizing the laminar and cellular architecture of PPC, its thalamic and cortical connections, and its positioning in relation to nearby cortical areas. Abstract The posterior parietal cortex (PPC) is a multifaceted region of cortex, contributing to several cognitive processes, including sensorimotor integration and spatial navigation. Although recent years have seen a considerable rise in the use of rodents, particularly mice, to investigate PPC and related networks, a coherent anatomical definition of PPC in the mouse is still lacking. To address this, we delineated the mouse PPC, using cyto‐ and chemoarchitectural markers from Nissl‐, parvalbumin‐and muscarinic acetylcholine receptor M2‐staining. Additionally, we performed bilateral triple anterograde tracer injections in primary visual cortex (V1) and prepared flattened tangential sections from one hemisphere and coronal sections from the other, allowing us to co‐register the cytoarchitectural features of PPC with V1 projections. This revealed that extrastriate area A was largely contained within lateral PPC, that medial PPC overlapped with the anterior portion of area AM, and that anterior RL overlapped partially with area PtP. Furthermore, triple anterograde tracer injections in PPC showed strong projections to associative thalamic nuclei as well as higher visual areas, orbitofrontal, cingulate and secondary motor cortices. Retrograde circuit mapping with rabies virus further showed that all cortical connections were reciprocal. These combined approaches provide a coherent definition of mouse PPC that incorporates laminar architecture, extrastriate projections, thalamic, and cortico–cortical connections. Karoline Hovde, Michele Gianatti, Menno P. Witter, Jonathan R. Whitlock https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14280?af=R European Journal of Neuroscience Architecture and organization of mouse posterior parietal cortex relative to extrastriate areas

The posterior parietal cortex (PPC) is a multifaceted region of cortex supporting several cognitive functions. Recent years have seen an increase in the use of rodents to study PPC, but a coherent definition of PPC in mice is still lacking. We addressed this by characterizing the laminar and cellular architecture of PPC, its thalamic and cortical connections, and its positioning in relation to nearby cortical areas.

 

Abstract

The posterior parietal cortex (PPC) is a multifaceted region of cortex, contributing to several cognitive processes, including sensorimotor integration and spatial navigation. Although recent years have seen a considerable rise in the use of rodents, particularly mice, to investigate PPC and related networks, a coherent anatomical definition of PPC in the mouse is still lacking. To address this, we delineated the mouse PPC, using cyto‐ and chemoarchitectural markers from Nissl‐, parvalbumin‐and muscarinic acetylcholine receptor M2‐staining. Additionally, we performed bilateral triple anterograde tracer injections in primary visual cortex (V1) and prepared flattened tangential sections from one hemisphere and coronal sections from the other, allowing us to co‐register the cytoarchitectural features of PPC with V1 projections. This revealed that extrastriate area A was largely contained within lateral PPC, that medial PPC overlapped with the anterior portion of area AM, and that anterior RL overlapped partially with area PtP. Furthermore, triple anterograde tracer injections in PPC showed strong projections to associative thalamic nuclei as well as higher visual areas, orbitofrontal, cingulate and secondary motor cortices. Retrograde circuit mapping with rabies virus further showed that all cortical connections were reciprocal. These combined approaches provide a coherent definition of mouse PPC that incorporates laminar architecture, extrastriate projections, thalamic, and cortico–cortical connections.

European Journal of Neuroscience, EarlyView. Architecture and organization of mouse posterior parietal cortex relative to extrastriate areas doi:10.1111/ejn.14280 European Journal of Neuroscience 2018-12-14T01:17:20-08:00 European Journal of Neuroscience 10.1111/ejn.14280 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14280?af=R RESEARCH REPORT Financial gain‐ and loss‐related BOLD signals in the human ventral tegmental area and substantia nigra pars compacta Imaging the ventral midbrain in humans is challenging because of its small size and vulnerability to physiological noise. In this study, we used functional magnetic resonance imaging (fMRI) methods optimized specifically for the midbrain (including high‐resolution imaging, a novel registration protocol, and physiological noise modelling) to reveal responses to financial gain and loss in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNC). Abstract Neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNC) play central roles in reward‐related behaviours. Nonhuman animal studies suggest that these neurons also process aversive events. However, our understanding of how the human VTA and SNC responds to such events is limited and has been hindered by the technical challenge of using functional magnetic resonance imaging (fMRI) to investigate a small structure where the signal is particularly vulnerable to physiological noise. Here we show, using methods optimized specifically for the midbrain (including high‐resolution imaging, a novel registration protocol, and physiological noise modelling), a BOLD (blood‐oxygen‐level dependent) signal to both financial gain and loss in the VTA and SNC, along with a response to nil outcomes that are better or worse than expected in the VTA. Taken together, these findings suggest that the human VTA and SNC are involved in the processing of both appetitive and aversive financial outcomes in humans. Eve H. Limbrick‐Oldfield, Robert Leech, Richard J. S. Wise, Mark A. Ungless https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14288?af=R European Journal of Neuroscience Financial gain‐ and loss‐related BOLD signals in the human ventral tegmental area and substantia nigra pars compacta

Imaging the ventral midbrain in humans is challenging because of its small size and vulnerability to physiological noise. In this study, we used functional magnetic resonance imaging (fMRI) methods optimized specifically for the midbrain (including high‐resolution imaging, a novel registration protocol, and physiological noise modelling) to reveal responses to financial gain and loss in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNC).

 

Abstract

Neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNC) play central roles in reward‐related behaviours. Nonhuman animal studies suggest that these neurons also process aversive events. However, our understanding of how the human VTA and SNC responds to such events is limited and has been hindered by the technical challenge of using functional magnetic resonance imaging (fMRI) to investigate a small structure where the signal is particularly vulnerable to physiological noise. Here we show, using methods optimized specifically for the midbrain (including high‐resolution imaging, a novel registration protocol, and physiological noise modelling), a BOLD (blood‐oxygen‐level dependent) signal to both financial gain and loss in the VTA and SNC, along with a response to nil outcomes that are better or worse than expected in the VTA. Taken together, these findings suggest that the human VTA and SNC are involved in the processing of both appetitive and aversive financial outcomes in humans.

European Journal of Neuroscience, EarlyView. Financial gain‐ and loss‐related BOLD signals in the human ventral tegmental area and substantia nigra pars compacta doi:10.1111/ejn.14288 European Journal of Neuroscience 2018-12-13T04:27:17-08:00 European Journal of Neuroscience 10.1111/ejn.14288 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14288?af=R RESEARCH REPORT Strategies to decrease social jetlag: Reducing evening blue light advances sleep and melatonin Social jetlag (SJL) is a measure of the discrepancy between circadian (internal) and social (external) clocks. SJL has been associated with widespread, population diseases. Here we tested two protocols involving in‐home light interventions in order to reduce SJL. We found that decreasing evening blue light advanced sleep onset and melatonin secretion, however, SJL was not reduced. Abstract The timing of sleep is under the control of the circadian clock, which uses light to entrain to the external light‐dark cycle. A combination of genetic, physiological and environmental factors produces individual differences in chronotype (entrained phase as manifest in sleep timing). A mismatch between circadian and societal (e.g., work) clocks leads to a condition called social jetlag, which is characterized by changing sleep times over work and free days and accumulation of sleep debt. Social jetlag, which is prevalent in late chronotypes, has been related to several health issues. One way to reduce social jetlag would be to advance the circadian clock via modifications of the light environment. We thus performed two intervention field studies to describe methods for decreasing social jetlag. One study decreased evening light exposure (via blue‐light‐blocking glasses) and the other used increased morning light (via the use of curtains). We measured behaviour as well as melatonin; the latter in order to validate that behaviour was consistent with this neuroendocrinological phase marker of the circadian clock. We found that a decrease in evening blue light exposure led to an advance in melatonin and sleep onset on workdays. Increased morning light exposure advanced neither melatonin secretion nor sleep timing. Neither protocol led to a significant change in social jetlag. Despite this, our findings show that controlling light exposure at home can be effective in advancing melatonin secretion and sleep, thereby helping late chronotypes to better cope with early social schedules. Giulia Zerbini, Thomas Kantermann, Martha Merrow https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14293?af=R European Journal of Neuroscience Strategies to decrease social jetlag: Reducing evening blue light advances sleep and melatonin

Social jetlag (SJL) is a measure of the discrepancy between circadian (internal) and social (external) clocks. SJL has been associated with widespread, population diseases. Here we tested two protocols involving in‐home light interventions in order to reduce SJL. We found that decreasing evening blue light advanced sleep onset and melatonin secretion, however, SJL was not reduced.

 

Abstract

The timing of sleep is under the control of the circadian clock, which uses light to entrain to the external light‐dark cycle. A combination of genetic, physiological and environmental factors produces individual differences in chronotype (entrained phase as manifest in sleep timing). A mismatch between circadian and societal (e.g., work) clocks leads to a condition called social jetlag, which is characterized by changing sleep times over work and free days and accumulation of sleep debt. Social jetlag, which is prevalent in late chronotypes, has been related to several health issues. One way to reduce social jetlag would be to advance the circadian clock via modifications of the light environment. We thus performed two intervention field studies to describe methods for decreasing social jetlag. One study decreased evening light exposure (via blue‐light‐blocking glasses) and the other used increased morning light (via the use of curtains). We measured behaviour as well as melatonin; the latter in order to validate that behaviour was consistent with this neuroendocrinological phase marker of the circadian clock. We found that a decrease in evening blue light exposure led to an advance in melatonin and sleep onset on workdays. Increased morning light exposure advanced neither melatonin secretion nor sleep timing. Neither protocol led to a significant change in social jetlag. Despite this, our findings show that controlling light exposure at home can be effective in advancing melatonin secretion and sleep, thereby helping late chronotypes to better cope with early social schedules.

European Journal of Neuroscience, EarlyView. Strategies to decrease social jetlag: Reducing evening blue light advances sleep and melatonin doi:10.1111/ejn.14293 European Journal of Neuroscience 2018-12-13T04:25:55-08:00 European Journal of Neuroscience 10.1111/ejn.14293 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14293?af=R SPECIAL ISSUE ARTICLE The relationship between the temporal structure of magnetoencephalography recorded brain activity and capacity to form discrete auditory representations Rates at which auditory stimuli could be discretely represented matched oscillatory brain activity over a range of frequencies. Oscillations also entrained to stimuli and a series of gamma band events, involving phase and amplitude, predicted successful discrete representation. These findings support the proposal that oscillations may align activity to provide limited conditions for representational neuronal assemblies across a range of frequencies. Abstract A function of oscillatory brain activity may be to align activity relative to threshold potentials and in doing so provide limited opportunities for representational neuronal assemblies to form. This low‐level function could apply across frequency bands and potentially affect the temporal dynamics of experience. To test these possibilities, a magnetoencephalography protocol was developed where capacity to form discrete auditory representations over time was assessed relative to oscillatory brain activity. Three sets of preregistered analyses were conducted. First, the capacity to form representations correlated with the prevalence and durations of activity localised to the auditory cortex. Second, brain oscillations became entrained to stimuli over a broad range of frequencies. Finally, a sequence of gamma (γ) band events predicted successful discrete representation, where previous research had indicated similar individuation‐related differences within the alpha (α) range. Together, these findings indicate that a low‐level function of cortical oscillations, which may apply across a range of frequency bands, is periodically to set conditions in which representational neuronal assemblies can manifest, limiting and so affecting the flow of experience. Christopher Allen https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14289?af=R European Journal of Neuroscience The relationship between the temporal structure of magnetoencephalography recorded brain activity and capacity to form discrete auditory representations

Rates at which auditory stimuli could be discretely represented matched oscillatory brain activity over a range of frequencies. Oscillations also entrained to stimuli and a series of gamma band events, involving phase and amplitude, predicted successful discrete representation. These findings support the proposal that oscillations may align activity to provide limited conditions for representational neuronal assemblies across a range of frequencies.

 

Abstract

A function of oscillatory brain activity may be to align activity relative to threshold potentials and in doing so provide limited opportunities for representational neuronal assemblies to form. This low‐level function could apply across frequency bands and potentially affect the temporal dynamics of experience. To test these possibilities, a magnetoencephalography protocol was developed where capacity to form discrete auditory representations over time was assessed relative to oscillatory brain activity. Three sets of preregistered analyses were conducted. First, the capacity to form representations correlated with the prevalence and durations of activity localised to the auditory cortex. Second, brain oscillations became entrained to stimuli over a broad range of frequencies. Finally, a sequence of gamma (γ) band events predicted successful discrete representation, where previous research had indicated similar individuation‐related differences within the alpha (α) range. Together, these findings indicate that a low‐level function of cortical oscillations, which may apply across a range of frequency bands, is periodically to set conditions in which representational neuronal assemblies can manifest, limiting and so affecting the flow of experience.

European Journal of Neuroscience, EarlyView. The relationship between the temporal structure of magnetoencephalography recorded brain activity and capacity to form discrete auditory representations doi:10.1111/ejn.14289 European Journal of Neuroscience 2018-12-11T08:34:50-08:00 European Journal of Neuroscience 10.1111/ejn.14289 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14289?af=R RESEARCH REPORT Task‐dependent responses to muscle vibration during reaching Muscle vibration perturbs the estimated reach trajectory, not the actual trajectory. We show that responses to vibration become task‐dependent with a latency of about 100 ms, similar to responses to stretch perturbations. These observations help us understand the mechanisms that contribute to fast, yet purposeful, responses to unforeseen stimuli. Abstract Feedback corrections in reaching have been shown to be task‐dependent for proprioceptive, visual and vestibular perturbations, in line with predictions from optimal feedback control theory. Mechanical perturbations have been used to elicit proprioceptive errors, but have the drawback to actively alter the limb's trajectory, making it nontrivial to dissociate the subject's compensatory response from the perturbation itself. In contrast, muscle vibration provides an alternative tool to perturb the muscle afferents without changing the hands trajectory, inducing only changes in the estimated, but not the actual, limb position and velocity. Here, we investigate whether upper‐arm muscle vibration is sufficient to evoke task‐dependent feedback corrections during goal‐directed reaching to a narrow versus a wide target. Our main result is that for vibration of biceps and triceps, compensatory responses were down‐regulated for the wide compared to the narrow target. The earliest detectable difference between these target‐specific corrections is at about 100 ms, likely reflecting a task‐dependent feedback control policy rather than a voluntary response. Johannes Keyser, Rob E. F. S. Ramakers, W. Pieter Medendorp, Luc P. J. Selen https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14292?af=R European Journal of Neuroscience Task‐dependent responses to muscle vibration during reaching

Muscle vibration perturbs the estimated reach trajectory, not the actual trajectory. We show that responses to vibration become task‐dependent with a latency of about 100 ms, similar to responses to stretch perturbations. These observations help us understand the mechanisms that contribute to fast, yet purposeful, responses to unforeseen stimuli.

 

Abstract

Feedback corrections in reaching have been shown to be task‐dependent for proprioceptive, visual and vestibular perturbations, in line with predictions from optimal feedback control theory. Mechanical perturbations have been used to elicit proprioceptive errors, but have the drawback to actively alter the limb's trajectory, making it nontrivial to dissociate the subject's compensatory response from the perturbation itself. In contrast, muscle vibration provides an alternative tool to perturb the muscle afferents without changing the hands trajectory, inducing only changes in the estimated, but not the actual, limb position and velocity. Here, we investigate whether upper‐arm muscle vibration is sufficient to evoke task‐dependent feedback corrections during goal‐directed reaching to a narrow versus a wide target. Our main result is that for vibration of biceps and triceps, compensatory responses were down‐regulated for the wide compared to the narrow target. The earliest detectable difference between these target‐specific corrections is at about 100 ms, likely reflecting a task‐dependent feedback control policy rather than a voluntary response.

European Journal of Neuroscience, EarlyView. Task‐dependent responses to muscle vibration during reaching doi:10.1111/ejn.14292 European Journal of Neuroscience 2018-12-11T02:10:07-08:00 European Journal of Neuroscience 10.1111/ejn.14292 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14292?af=R RESEARCH REPORT Insulin in the ventral tegmental area reduces cocaine‐evoked dopamine in the nucleus accumbens in vivo Insulin acting at insulin receptors in the ventral tegmental area (VTA) suppresses pedunculopontine nucleus‐evoked dopamine or cocaine‐potentiated dopamine in the nucleus accumbens core. Intra‐VTA or intranasal insulin decreased locomotor responses to cocaine, an effect blocked by an intra‐VTA administered insulin receptor antagonist. Abstract Mesolimbic dopamine circuits, implicated in incentive motivation, are sensitive to changes in metabolic state such as weight loss and diet‐induced obesity. These neurons are important targets for metabolic hormones such as leptin, glucagon‐like peptide‐1, ghrelin and insulin. Insulin receptors are located on dopamine neurons in the ventral tegmental area (VTA) and we have previously demonstrated that insulin induces long‐term depression of excitatory synapses onto VTA dopamine neurons. While insulin can decrease dopamine concentration in somatodendritic regions, it can increase dopamine in striatal slices. Whether insulin directly targets the VTA to alter dopamine release in projection areas, such as the nucleus accumbens (NAc), remains unknown. The main goal of the present experiments was to examine NAc dopamine concentration following VTA administration of insulin. Using in vivo FSCV to detect rapid fluctuations in dopamine concentration, we showed that intra‐VTA insulin via action at insulin receptors reduced pedunculopontine nucleus‐evoked dopamine release in the NAc. Furthermore, intra‐VTA insulin reduced cocaine‐potentiated NAc dopamine. Finally, intra‐VTA or intranasal insulin decreased locomotor responses to cocaine, an effect blocked by an intra‐VTA administered insulin receptor antagonist. Together, these data demonstrate that mesolimbic dopaminergic projections are important targets of the metabolic hormone, insulin. Lindsay Naef, Lauren Seabrook, Jeff Hsiao, Calvin Li, Stephanie L. Borgland https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14291?af=R European Journal of Neuroscience Insulin in the ventral tegmental area reduces cocaine‐evoked dopamine in the nucleus accumbens in vivo

Insulin acting at insulin receptors in the ventral tegmental area (VTA) suppresses pedunculopontine nucleus‐evoked dopamine or cocaine‐potentiated dopamine in the nucleus accumbens core. Intra‐VTA or intranasal insulin decreased locomotor responses to cocaine, an effect blocked by an intra‐VTA administered insulin receptor antagonist.

 

Abstract

Mesolimbic dopamine circuits, implicated in incentive motivation, are sensitive to changes in metabolic state such as weight loss and diet‐induced obesity. These neurons are important targets for metabolic hormones such as leptin, glucagon‐like peptide‐1, ghrelin and insulin. Insulin receptors are located on dopamine neurons in the ventral tegmental area (VTA) and we have previously demonstrated that insulin induces long‐term depression of excitatory synapses onto VTA dopamine neurons. While insulin can decrease dopamine concentration in somatodendritic regions, it can increase dopamine in striatal slices. Whether insulin directly targets the VTA to alter dopamine release in projection areas, such as the nucleus accumbens (NAc), remains unknown. The main goal of the present experiments was to examine NAc dopamine concentration following VTA administration of insulin. Using in vivo FSCV to detect rapid fluctuations in dopamine concentration, we showed that intra‐VTA insulin via action at insulin receptors reduced pedunculopontine nucleus‐evoked dopamine release in the NAc. Furthermore, intra‐VTA insulin reduced cocaine‐potentiated NAc dopamine. Finally, intra‐VTA or intranasal insulin decreased locomotor responses to cocaine, an effect blocked by an intra‐VTA administered insulin receptor antagonist. Together, these data demonstrate that mesolimbic dopaminergic projections are important targets of the metabolic hormone, insulin.

European Journal of Neuroscience, EarlyView. Insulin in the ventral tegmental area reduces cocaine‐evoked dopamine in the nucleus accumbens in vivo doi:10.1111/ejn.14291 European Journal of Neuroscience 2018-12-11T02:00:15-08:00 European Journal of Neuroscience 10.1111/ejn.14291 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14291?af=R Special Issue Article Interactions between monoamine oxidase A rs1137070 and smoking on brain structure and function in male smokers We investigated the interactions between MAOA rs1137070 and smoking on the brain structure and function by using gray matter volume and functional connectivity strength measurements. Such interactions were observed on the OFC, hippocampus, left dorsolateral prefrontal cortex and IPL. Our findings suggest that MAOA rs1137070 contributes to the susceptibility to nicotine dependence through its influence on brain circuits involved in reward and attention, and interacts with smoking in the progression. Abstract The monoamine oxidase A (MAOA) enzyme metabolizes monoamine neurotransmitters such as dopamine, serotonin and norepinephrine, and its genetic polymorphism (rs1137070) influences its activity level and is associated with smoking behaviors. However, the underlying neural mechanisms of the gene × environment interactions remain largely unknown. In this study, we aimed to explore the interactive effects of the rs1137070 and cigarette smoking on gray matter volume (GMV) and functional connectivity strength (FCS). A total of 81 smokers and 42 nonsmokers were enrolled in the present study. Voxel‐based morphometry analysis showed a significant rs1137070 genotype × smoking effect on the GMV of the left orbitofrontal cortex (OFC), such that individuals with risk allele had greater GMV among nonsmokers but not smokers. Meanwhile, rs1137070 variant and nicotine dependence interactively altered the FCS of the right hippocampus, the left inferior parietal lobule (IPL), the left dorsolateral prefrontal cortex and bilateral OFC. In addition, the FCS in the left IPL was correlated with smoking initiation and smoking years in smokers with the risk allele. These findings suggest that MAOA rs1137070 contributes to the susceptibility to nicotine dependence through its influence on brain circuits involved in reward and attention, and interacts with smoking in the progression. Zhujing Shen, Peiyu Huang, Chao Wang, Wei Qian, Xiao Luo, Quanquan Gu, Huan Chen, Hongjuan Wang, Yihong Yang, Minming Zhang https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14282?af=R European Journal of Neuroscience Interactions between monoamine oxidase A rs1137070 and smoking on brain structure and function in male smokers

We investigated the interactions between MAOA rs1137070 and smoking on the brain structure and function by using gray matter volume and functional connectivity strength measurements. Such interactions were observed on the OFC, hippocampus, left dorsolateral prefrontal cortex and IPL. Our findings suggest that MAOA rs1137070 contributes to the susceptibility to nicotine dependence through its influence on brain circuits involved in reward and attention, and interacts with smoking in the progression.

 

Abstract

The monoamine oxidase A (MAOA) enzyme metabolizes monoamine neurotransmitters such as dopamine, serotonin and norepinephrine, and its genetic polymorphism (rs1137070) influences its activity level and is associated with smoking behaviors. However, the underlying neural mechanisms of the gene × environment interactions remain largely unknown. In this study, we aimed to explore the interactive effects of the rs1137070 and cigarette smoking on gray matter volume (GMV) and functional connectivity strength (FCS). A total of 81 smokers and 42 nonsmokers were enrolled in the present study. Voxel‐based morphometry analysis showed a significant rs1137070 genotype × smoking effect on the GMV of the left orbitofrontal cortex (OFC), such that individuals with risk allele had greater GMV among nonsmokers but not smokers. Meanwhile, rs1137070 variant and nicotine dependence interactively altered the FCS of the right hippocampus, the left inferior parietal lobule (IPL), the left dorsolateral prefrontal cortex and bilateral OFC. In addition, the FCS in the left IPL was correlated with smoking initiation and smoking years in smokers with the risk allele. These findings suggest that MAOA rs1137070 contributes to the susceptibility to nicotine dependence through its influence on brain circuits involved in reward and attention, and interacts with smoking in the progression.

European Journal of Neuroscience, EarlyView. Interactions between monoamine oxidase A rs1137070 and smoking on brain structure and function in male smokers doi:10.1111/ejn.14282 European Journal of Neuroscience 2018-12-11T01:28:33-08:00 European Journal of Neuroscience 10.1111/ejn.14282 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14282?af=R Special Issue Article Immune system responses in Parkinson's disease: Early and dynamic Clinical and basic research has revealed the involvement of both the innate and adaptive immune systems in Parkinson's disease (PD). PD leads not only to a microglia response in brain, but also to a cellular and humoral peripheral immune response. This has resulted into the current understanding of the immune response in PD, which is proposed to occur early, involve peripheral and brain immune cells, evolve as neuronal dysfunction progresses, and is likely to influence disease progression. Abstract The neuropathological hallmarks of Parkinson's disease (PD) are the degeneration and death of dopamine‐producing neurons in the ventral midbrain, the widespread intraneuronal aggregation of alpha‐synuclein (α) in Lewy bodies and neurites, neuroinflammation, and gliosis. Signs of microglia activation in the PD brain postmortem as well as during disease development revealed by neuroimaging, implicate immune responses in the pathophysiology of the disease. Intensive research during the last two decades has advanced our understanding of the role of these responses in the disease process, yet many questions remain unanswered. A transformative finding in the field has been the confirmation that in vivo microglia are able to respond directly to pathological a‐syn aggregates but also to neuronal dysfunction due to intraneuronal a‐syn toxicity well in advance of neuronal death. In addition, clinical research and disease models have revealed the involvement of both the innate and adaptive immune systems. Indeed, the data suggest that PD leads not only to a microglia response, but also to a cellular and humoral peripheral immune response. Together, these findings compel us to consider a more holistic view of the immunological processes associated with the disease. Central and peripheral immune responses aimed at maintaining neuronal health will ultimately have consequences on neuronal survival. We will review here the most significant findings that have contributed to the current understanding of the immune response in PD, which is proposed to occur early, involve peripheral and brain immune cells, evolve as neuronal dysfunction progresses, and is likely to influence disease progression. Malú G. Tansey, Marina Romero‐Ramos https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14290?af=R European Journal of Neuroscience Immune system responses in Parkinson's disease: Early and dynamic

Clinical and basic research has revealed the involvement of both the innate and adaptive immune systems in Parkinson's disease (PD). PD leads not only to a microglia response in brain, but also to a cellular and humoral peripheral immune response. This has resulted into the current understanding of the immune response in PD, which is proposed to occur early, involve peripheral and brain immune cells, evolve as neuronal dysfunction progresses, and is likely to influence disease progression.

 

Abstract

The neuropathological hallmarks of Parkinson's disease (PD) are the degeneration and death of dopamine‐producing neurons in the ventral midbrain, the widespread intraneuronal aggregation of alpha‐synuclein (α) in Lewy bodies and neurites, neuroinflammation, and gliosis. Signs of microglia activation in the PD brain postmortem as well as during disease development revealed by neuroimaging, implicate immune responses in the pathophysiology of the disease. Intensive research during the last two decades has advanced our understanding of the role of these responses in the disease process, yet many questions remain unanswered. A transformative finding in the field has been the confirmation that in vivo microglia are able to respond directly to pathological a‐syn aggregates but also to neuronal dysfunction due to intraneuronal a‐syn toxicity well in advance of neuronal death. In addition, clinical research and disease models have revealed the involvement of both the innate and adaptive immune systems. Indeed, the data suggest that PD leads not only to a microglia response, but also to a cellular and humoral peripheral immune response. Together, these findings compel us to consider a more holistic view of the immunological processes associated with the disease. Central and peripheral immune responses aimed at maintaining neuronal health will ultimately have consequences on neuronal survival. We will review here the most significant findings that have contributed to the current understanding of the immune response in PD, which is proposed to occur early, involve peripheral and brain immune cells, evolve as neuronal dysfunction progresses, and is likely to influence disease progression.

European Journal of Neuroscience, EarlyView. Immune system responses in Parkinson's disease: Early and dynamic doi:10.1111/ejn.14290 European Journal of Neuroscience 2018-12-10T02:04:29-08:00 European Journal of Neuroscience 10.1111/ejn.14290 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14290?af=R SPECIAL ISSUE REVIEW Striatal GABAergic interneuron dysfunction in the Q175 mouse model of Huntington's disease In symptomatic (12 month) Q175 HD mice, striatal fast‐spiking interneurons undergo changes in passive and active membrane properties, as well as morphological changes, whereas a subpopulation of low‐threshold spiking interneurons display an increase in action potential firing within oscillating bursts but no change in membrane properties. The data presented in this manuscript suggest the HD mutation differentially affects the membrane and synaptic properties of these two classes of GABAergic interneurons, as well as their ability to respond to compensatory challenges presented during the late stage of the disease. Abstract The pathological hallmark of Huntington's disease (HD) is the massive loss of striatal and cortical neurons. Until recently, it was believed that striatal interneurons were spared from degeneration. This view has changed after the demonstration that parvalbumin (PV)‐expressing interneurons also are vulnerable in humans. Here we compared morphological and functional changes of striatal fast‐spiking interneurons (FSIs) and low‐threshold spiking (LTS) interneurons in the Q175 mouse model of HD at presymptomatic (2 months) and symptomatic (12 months) stages of the disease. Electrophysiological intrinsic and synaptic properties of FSIs were significantly altered in symptomatic mice compared to wild‐type (WT) littermates. Overall, FSIs became more excitable with disease progression. Sholl analysis also revealed a significant loss of dendritic complexity and excitatory synaptic inputs. The basic membrane and synaptic properties of LTS interneurons were similar in Q175 and WT mice regardless of disease stage. The resilience of LTS interneurons could be related to their sparsity of excitatory synaptic inputs compared with FSIs. However, in symptomatic mice, a subpopulation of LTS interneurons displayed an increase in action potential firing within oscillating bursts. Thus, we conclude that while both FSI and LTS interneurons demonstrate increases in excitability, the HD mutation differentially affects their membrane and synaptic properties as well as their ability to respond to compensatory challenges presented during the late stage of the disease. Alterations in GABAergic interneuron intrinsic activity and responsiveness to incoming signals may significantly affect SPN output thus contributing to abnormal motor movements in patients afflicted with HD. Sandra M. Holley, Laurie Galvan, Talia Kamdjou, Carlos Cepeda, Michael S. Levine https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14283?af=R European Journal of Neuroscience Striatal GABAergic interneuron dysfunction in the Q175 mouse model of Huntington's disease

In symptomatic (12 month) Q175 HD mice, striatal fast‐spiking interneurons undergo changes in passive and active membrane properties, as well as morphological changes, whereas a subpopulation of low‐threshold spiking interneurons display an increase in action potential firing within oscillating bursts but no change in membrane properties. The data presented in this manuscript suggest the HD mutation differentially affects the membrane and synaptic properties of these two classes of GABAergic interneurons, as well as their ability to respond to compensatory challenges presented during the late stage of the disease.

 

Abstract

The pathological hallmark of Huntington's disease (HD) is the massive loss of striatal and cortical neurons. Until recently, it was believed that striatal interneurons were spared from degeneration. This view has changed after the demonstration that parvalbumin (PV)‐expressing interneurons also are vulnerable in humans. Here we compared morphological and functional changes of striatal fast‐spiking interneurons (FSIs) and low‐threshold spiking (LTS) interneurons in the Q175 mouse model of HD at presymptomatic (2 months) and symptomatic (12 months) stages of the disease. Electrophysiological intrinsic and synaptic properties of FSIs were significantly altered in symptomatic mice compared to wild‐type (WT) littermates. Overall, FSIs became more excitable with disease progression. Sholl analysis also revealed a significant loss of dendritic complexity and excitatory synaptic inputs. The basic membrane and synaptic properties of LTS interneurons were similar in Q175 and WT mice regardless of disease stage. The resilience of LTS interneurons could be related to their sparsity of excitatory synaptic inputs compared with FSIs. However, in symptomatic mice, a subpopulation of LTS interneurons displayed an increase in action potential firing within oscillating bursts. Thus, we conclude that while both FSI and LTS interneurons demonstrate increases in excitability, the HD mutation differentially affects their membrane and synaptic properties as well as their ability to respond to compensatory challenges presented during the late stage of the disease. Alterations in GABAergic interneuron intrinsic activity and responsiveness to incoming signals may significantly affect SPN output thus contributing to abnormal motor movements in patients afflicted with HD.

European Journal of Neuroscience, EarlyView. Striatal GABAergic interneuron dysfunction in the Q175 mouse model of Huntington's disease doi:10.1111/ejn.14283 European Journal of Neuroscience 2018-12-10T01:58:32-08:00 European Journal of Neuroscience 10.1111/ejn.14283 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14283?af=R RESEARCH REPORT Neuromodulation‐dependent effect of gated high‐frequency, LFMS‐like electric field stimulation in mouse cortical slices Low‐field magnetic stimulation (LFMS) is under investigation as a treatment for depression, but the electrophysiological and brain‐state dependent effects of this gated high‐frequency stimulation remains unknown. In the presence of cholinergic neuromodulation, LFMS‐like stimulation modulated neuronal firing in layer V after offset of the stimulation. These results demonstrate how neuromodulatory tone can determine the network response to brain stimulation. Abstract Low‐field magnetic stimulation (LFMS) is a gated high‐frequency non‐invasive brain stimulation method (500 Hz gated at 2 Hz) with a proposed antidepressant effect. However, it has remained unknown how such stimulation paradigms modulate neuronal network activity and how the induced changes depend on network state. Here we examined the immediate and outlasting effects of the gated high‐frequency electric field associated with LFMS on the cortical activity as a function of neuromodulatory tone that defines network state. We used a sham‐controlled study design to investigate effects of stimulation (20 min of 0.5 s trains of 500 Hz charge‐balanced pulse stimulation patterned at 0.5 Hz) on neural activity in mouse medial prefrontal cortex in vitro. Bath application of cholinergic and noradrenergic agents enabled us to examine the stimulation effects as a function of neuromodulatory tone. The stimulation attenuated the increase in firing rate of layer V cortical neurons during the post‐stimulation period in the presence of cholinergic activation. The same stimulation had no significant immediate or outlasting effect in the absence of exogenous neuromodulators or in the presence of noradrenergic activation. These results provide electrophysiological insights into the neuromodulatory‐dependent effects of gated high‐frequency stimulation. More broadly, our results are the first to provide a mechanistic demonstration of how behavioral states and arousal levels may modify the effects of non‐invasive brain stimulation. Ehsan Negahbani, Stephen L. Schmidt, Nadia Mishal, Flavio Fröhlich https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14273?af=R European Journal of Neuroscience Neuromodulation‐dependent effect of gated high‐frequency, LFMS‐like electric field stimulation in mouse cortical slices

Low‐field magnetic stimulation (LFMS) is under investigation as a treatment for depression, but the electrophysiological and brain‐state dependent effects of this gated high‐frequency stimulation remains unknown. In the presence of cholinergic neuromodulation, LFMS‐like stimulation modulated neuronal firing in layer V after offset of the stimulation. These results demonstrate how neuromodulatory tone can determine the network response to brain stimulation.

 

Abstract

Low‐field magnetic stimulation (LFMS) is a gated high‐frequency non‐invasive brain stimulation method (500 Hz gated at 2 Hz) with a proposed antidepressant effect. However, it has remained unknown how such stimulation paradigms modulate neuronal network activity and how the induced changes depend on network state. Here we examined the immediate and outlasting effects of the gated high‐frequency electric field associated with LFMS on the cortical activity as a function of neuromodulatory tone that defines network state. We used a sham‐controlled study design to investigate effects of stimulation (20 min of 0.5 s trains of 500 Hz charge‐balanced pulse stimulation patterned at 0.5 Hz) on neural activity in mouse medial prefrontal cortex in vitro. Bath application of cholinergic and noradrenergic agents enabled us to examine the stimulation effects as a function of neuromodulatory tone. The stimulation attenuated the increase in firing rate of layer V cortical neurons during the post‐stimulation period in the presence of cholinergic activation. The same stimulation had no significant immediate or outlasting effect in the absence of exogenous neuromodulators or in the presence of noradrenergic activation. These results provide electrophysiological insights into the neuromodulatory‐dependent effects of gated high‐frequency stimulation. More broadly, our results are the first to provide a mechanistic demonstration of how behavioral states and arousal levels may modify the effects of non‐invasive brain stimulation.

European Journal of Neuroscience, EarlyView. Neuromodulation‐dependent effect of gated high‐frequency, LFMS‐like electric field stimulation in mouse cortical slices doi:10.1111/ejn.14273 European Journal of Neuroscience 2018-12-10T01:43:56-08:00 European Journal of Neuroscience 10.1111/ejn.14273 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14273?af=R RESEARCH REPORT A novel tool for time‐locking study plans to results Pre‐RNG is a novel pre‐registration scheme that provides true time‐locking while being performed in‐lab, without the involvement of any third party. By using this scheme, researchers can guarantee that specific study plans and hypotheses have been specified before data acquisition, hence not after data exploration. Abstract Often researchers wish to mark an objective line between study plans that were specified before data acquisition and decisions that were made following data exploration. Contrary to common perception, registering study plans to an online platform prior to data collection does not by itself provide such an objective distinction, even when the registration is time‐stamped. Here, we adapt a method from the field of cryptography to allow encoding of study plans and predictions within random aspects of the data acquisition process. Doing so introduces a causal link between the preregistered content and objective attributes of the acquired data, such as the timing and location of brain activations. This guarantees that the preregistered plans and predictions are indeed specified prior to data collection. Our time‐locking system does not depend on any external party and can be performed entirely in‐lab. We provide code for easy implementation and a detailed example from the field of functional Magnetic Resonance Imaging (fMRI). Matan Mazor, Noam Mazor, Roy Mukamel https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14278?af=R European Journal of Neuroscience A novel tool for time‐locking study plans to results

Pre‐RNG is a novel pre‐registration scheme that provides true time‐locking while being performed in‐lab, without the involvement of any third party. By using this scheme, researchers can guarantee that specific study plans and hypotheses have been specified before data acquisition, hence not after data exploration.

 

Abstract

Often researchers wish to mark an objective line between study plans that were specified before data acquisition and decisions that were made following data exploration. Contrary to common perception, registering study plans to an online platform prior to data collection does not by itself provide such an objective distinction, even when the registration is time‐stamped. Here, we adapt a method from the field of cryptography to allow encoding of study plans and predictions within random aspects of the data acquisition process. Doing so introduces a causal link between the preregistered content and objective attributes of the acquired data, such as the timing and location of brain activations. This guarantees that the preregistered plans and predictions are indeed specified prior to data collection. Our time‐locking system does not depend on any external party and can be performed entirely in‐lab. We provide code for easy implementation and a detailed example from the field of functional Magnetic Resonance Imaging (fMRI).

European Journal of Neuroscience, EarlyView. A novel tool for time‐locking study plans to results doi:10.1111/ejn.14278 European Journal of Neuroscience 2018-12-10T01:18:05-08:00 European Journal of Neuroscience 10.1111/ejn.14278 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14278?af=R TECHNICAL SPOTLIGHT Nonhypoxic pharmacological stabilization of Hypoxia Inducible Factor 1α: Effects on dopaminergic differentiation of human neural stem cells Hypoxia‐induced stabilization of HIF‐1α has been shown to stimulate dopaminergic differentiation of stem cells and to protect against neurotoxins. We investigated the effects of noncompetitive and competitive HIF‐1α stabilizing compounds on the dopaminergic differentiation of human neural stem cells. Following HIF‐1α stabilization, the cultures displayed a reduced proliferative activity and contained significantly increased relative levels of tyrosine hydroxylase‐positive dopaminergic neurons. Abstract Parkinson's disease is a neurodegenerative disease resulting in degeneration of midbrain dopaminergic neurons. Exploratory studies using human foetal tissue or predifferentiated stem cells have suggested that intracerebral transplantation of dopaminergic precursor cells may become an effective treatment for patients with Parkinson's disease. However, strategies for dopaminergic stem cell differentiation vary widely in efficiency, and better methods still need to be developed. Hypoxia Inducible Factor 1 (HIF‐1) is a transcription factor involved in the regulation of genes important for cellular adaption to hypoxia and low glucose supply. HIF‐1 is to a large degree regulated by the availability of oxygen as in its presence, the subunit HIF‐1α is degraded by HIF prolyl hydroxylase enzymes (HPHs). Stabilization of HIF‐1α through inhibition of HPHs has been shown to increase dopaminergic differentiation of stem cells and to protect dopaminergic neurons against neurotoxins. This study investigated the effects of noncompetitive (FG‐0041) and competitive (Compound A and JNJ‐42041935) HIF‐1α stabilizing compounds on the dopaminergic differentiation of human neural stem cells. Treatment with all HPH inhibitors at high oxygen tension (20%) resulted in HIF‐1α stabilization as assessed by immunocytochemistry for HIF‐1α and detection of increased levels of vascular endothelial growth factor in the conditioned culture medium. Following 10 days of HIF‐1α stabilization, the cultures displayed a slightly reduced proliferative activity and significantly increased relative levels of tyrosine hydroxylase‐positive dopaminergic neurons. In conclusion, HIF‐1α stabilization may represent a promising strategy for the generation of dopaminergic neurons intended for use in experimental in vitro studies and cell replacement therapies. Sabine Morris Hey, Pia Jensen, Matias Ryding, Alberto Martínez Serrano, Bjarne W. Kristensen, Morten Meyer https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14284?af=R European Journal of Neuroscience Nonhypoxic pharmacological stabilization of Hypoxia Inducible Factor 1α: Effects on dopaminergic differentiation of human neural stem cells

Hypoxia‐induced stabilization of HIF‐1α has been shown to stimulate dopaminergic differentiation of stem cells and to protect against neurotoxins. We investigated the effects of noncompetitive and competitive HIF‐1α stabilizing compounds on the dopaminergic differentiation of human neural stem cells. Following HIF‐1α stabilization, the cultures displayed a reduced proliferative activity and contained significantly increased relative levels of tyrosine hydroxylase‐positive dopaminergic neurons.

 

Abstract

Parkinson's disease is a neurodegenerative disease resulting in degeneration of midbrain dopaminergic neurons. Exploratory studies using human foetal tissue or predifferentiated stem cells have suggested that intracerebral transplantation of dopaminergic precursor cells may become an effective treatment for patients with Parkinson's disease. However, strategies for dopaminergic stem cell differentiation vary widely in efficiency, and better methods still need to be developed. Hypoxia Inducible Factor 1 (HIF‐1) is a transcription factor involved in the regulation of genes important for cellular adaption to hypoxia and low glucose supply. HIF‐1 is to a large degree regulated by the availability of oxygen as in its presence, the subunit HIF‐1α is degraded by HIF prolyl hydroxylase enzymes (HPHs). Stabilization of HIF‐1α through inhibition of HPHs has been shown to increase dopaminergic differentiation of stem cells and to protect dopaminergic neurons against neurotoxins. This study investigated the effects of noncompetitive (FG‐0041) and competitive (Compound A and JNJ‐42041935) HIF‐1α stabilizing compounds on the dopaminergic differentiation of human neural stem cells. Treatment with all HPH inhibitors at high oxygen tension (20%) resulted in HIF‐1α stabilization as assessed by immunocytochemistry for HIF‐1α and detection of increased levels of vascular endothelial growth factor in the conditioned culture medium. Following 10 days of HIF‐1α stabilization, the cultures displayed a slightly reduced proliferative activity and significantly increased relative levels of tyrosine hydroxylase‐positive dopaminergic neurons. In conclusion, HIF‐1α stabilization may represent a promising strategy for the generation of dopaminergic neurons intended for use in experimental in vitro studies and cell replacement therapies.

European Journal of Neuroscience, EarlyView. Nonhypoxic pharmacological stabilization of Hypoxia Inducible Factor 1α: Effects on dopaminergic differentiation of human neural stem cells doi:10.1111/ejn.14284 European Journal of Neuroscience 2018-12-08T09:33:25-08:00 European Journal of Neuroscience 10.1111/ejn.14284 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14284?af=R SPECIAL ISSUE ARTICLE Periodicity, repression, and the molecular architecture of the mammalian circadian clock Structural and biochemical analyses have uncovered a number of key features of the proteins that form the basis of circadian timing in vertebrates. In particular, a repeating motif in protein–protein interactions within the clockwork is shared, competitive interfaces. Here, we review major findings and make the case that competition at these sites between coactivators and repressors drives oscillatory gene expression and represents a key node for the regulation of periodicity within the clock. Abstract Large molecular machines regulate daily cycles of transcriptional activity and help generate rhythmic behavior. In recent years, structural and biochemical analyses have elucidated a number of principles guiding the interactions of proteins that form the basis of circadian timing. In its simplest form, the circadian clock is composed of a transcription/translation feedback loop. However, this description elides a complicated process of activator recruitment, chromatin decompaction, recruitment of coactivators, expression of repressors, formation of a repressive complex, repression of the activators, and ultimately degradation of the repressors and reinitiation of the cycle. Understanding the core principles underlying the clock requires careful examination of molecular and even atomic level details of these processes. Here, we review major structural and biochemical findings in circadian biology and make the argument that shared protein interfaces within the clockwork are critical for both the generation of rhythmicity and timing of the clock. Clark Rosensweig, Carla B. Green https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14254?af=R European Journal of Neuroscience Periodicity, repression, and the molecular architecture of the mammalian circadian clock

Structural and biochemical analyses have uncovered a number of key features of the proteins that form the basis of circadian timing in vertebrates. In particular, a repeating motif in protein–protein interactions within the clockwork is shared, competitive interfaces. Here, we review major findings and make the case that competition at these sites between coactivators and repressors drives oscillatory gene expression and represents a key node for the regulation of periodicity within the clock.

 

Abstract

Large molecular machines regulate daily cycles of transcriptional activity and help generate rhythmic behavior. In recent years, structural and biochemical analyses have elucidated a number of principles guiding the interactions of proteins that form the basis of circadian timing. In its simplest form, the circadian clock is composed of a transcription/translation feedback loop. However, this description elides a complicated process of activator recruitment, chromatin decompaction, recruitment of coactivators, expression of repressors, formation of a repressive complex, repression of the activators, and ultimately degradation of the repressors and reinitiation of the cycle. Understanding the core principles underlying the clock requires careful examination of molecular and even atomic level details of these processes. Here, we review major structural and biochemical findings in circadian biology and make the argument that shared protein interfaces within the clockwork are critical for both the generation of rhythmicity and timing of the clock.

European Journal of Neuroscience, EarlyView. Periodicity, repression, and the molecular architecture of the mammalian circadian clock doi:10.1111/ejn.14254 European Journal of Neuroscience 2018-12-08T09:29:23-08:00 European Journal of Neuroscience 10.1111/ejn.14254 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14254?af=R SPECIAL ISSUE REVIEW Vagus nerve spiking activity associated with locomotion and cortical arousal states in a freely moving rat Vagus nerve spikes increased with locomotion and the increased activity was retained for several seconds. During stopping, the vagus nerve spike patterns differed depending on external contexts and peripheral activity states associated with cortical arousal levels. These results are a new step for uncovering the physiological dynamics of the vagus nerve. Abstract The vagus nerve serves as a central pathway for communication between the central and peripheral organs. Despite traditional knowledge of vagus nerve functions, detailed neurophysiological dynamics of the vagus nerve in naïve behavior remain to be understood. In this study, we developed a new method to record spiking patterns from the cervical vagus nerve while simultaneously monitoring central and peripheral organ bioelectrical signals in a freely moving rat. When the rats transiently elevated locomotor activity, the frequency of vagus nerve spikes was correspondingly increased, and this activity was retained for several seconds after the increase in running speed terminated. Spike patterns of the vagus nerve were not robustly associated with which arms the animals entered on an elevated plus maze. During sniffing behavior, vagus nerve spikes were nearly absent. During stopping, the vagus nerve spike patterns differed considerably depending on external contexts and peripheral activity states associated with cortical arousal levels. Stimulation of the vagus nerve altered rat's running speed and cortical arousal states depending on running speed at the instant of stimulation. These observations are a new step for uncovering the physiological dynamics of the vagus nerve modulating the visceral organs such as cardiovascular, respiratory, and gastrointestinal systems. Yu Shikano, Yuya Nishimura, Toya Okonogi, Yuji Ikegaya, Takuya Sasaki https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14275?af=R European Journal of Neuroscience Vagus nerve spiking activity associated with locomotion and cortical arousal states in a freely moving rat

Vagus nerve spikes increased with locomotion and the increased activity was retained for several seconds. During stopping, the vagus nerve spike patterns differed depending on external contexts and peripheral activity states associated with cortical arousal levels. These results are a new step for uncovering the physiological dynamics of the vagus nerve.

 

Abstract

The vagus nerve serves as a central pathway for communication between the central and peripheral organs. Despite traditional knowledge of vagus nerve functions, detailed neurophysiological dynamics of the vagus nerve in naïve behavior remain to be understood. In this study, we developed a new method to record spiking patterns from the cervical vagus nerve while simultaneously monitoring central and peripheral organ bioelectrical signals in a freely moving rat. When the rats transiently elevated locomotor activity, the frequency of vagus nerve spikes was correspondingly increased, and this activity was retained for several seconds after the increase in running speed terminated. Spike patterns of the vagus nerve were not robustly associated with which arms the animals entered on an elevated plus maze. During sniffing behavior, vagus nerve spikes were nearly absent. During stopping, the vagus nerve spike patterns differed considerably depending on external contexts and peripheral activity states associated with cortical arousal levels. Stimulation of the vagus nerve altered rat's running speed and cortical arousal states depending on running speed at the instant of stimulation. These observations are a new step for uncovering the physiological dynamics of the vagus nerve modulating the visceral organs such as cardiovascular, respiratory, and gastrointestinal systems.

European Journal of Neuroscience, EarlyView. Vagus nerve spiking activity associated with locomotion and cortical arousal states in a freely moving rat doi:10.1111/ejn.14275 European Journal of Neuroscience 2018-12-08T12:00:00-08:00 European Journal of Neuroscience 10.1111/ejn.14275 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14275?af=R RESEARCH REPORT Synchronization and maintenance of circadian timing in the mammalian clockwork The suprachiasmatic nucleus (SCN) is the master circadian pacemaker in mammals. Intercellular coupling of cell‐autonomous oscillators confers robustness, stability and amplitude to the circadian pacemaker. The SCN can be delineated into distinct subdivisions with a retino‐recipient core and dorsomedial shell regions. Recent advances in mouse intersectional genetics are enabling the understanding of the contribution of these heterogeneous neuronal populations in controlling SCN network properties. Abstract The hypothalamic suprachiasmatic nucleus (SCN) is the principal circadian pacemaker in mammals. Cells in the SCN contain cell‐autonomous transcriptional‐translational feedback loops, which are synchronised to each other and thereby provide a coherent output to direct synchrony of peripheral clocks located in the brain and body. A major difference between these peripheral clocks and the SCN is the requirement for intercellular coupling mechanisms, which confer robustness, stability and amplitude to the system. There has been remarkable progress to our understanding of the intra‐ and inter‐cellular mechanisms of the SCN circuitry over the last ~20 years, which has come hand‐in‐hand with the development of new technologies to measure and manipulate the clock. Elizabeth S. Maywood https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14279?af=R European Journal of Neuroscience Synchronization and maintenance of circadian timing in the mammalian clockwork

The suprachiasmatic nucleus (SCN) is the master circadian pacemaker in mammals. Intercellular coupling of cell‐autonomous oscillators confers robustness, stability and amplitude to the circadian pacemaker. The SCN can be delineated into distinct subdivisions with a retino‐recipient core and dorsomedial shell regions. Recent advances in mouse intersectional genetics are enabling the understanding of the contribution of these heterogeneous neuronal populations in controlling SCN network properties.

 

Abstract

The hypothalamic suprachiasmatic nucleus (SCN) is the principal circadian pacemaker in mammals. Cells in the SCN contain cell‐autonomous transcriptional‐translational feedback loops, which are synchronised to each other and thereby provide a coherent output to direct synchrony of peripheral clocks located in the brain and body. A major difference between these peripheral clocks and the SCN is the requirement for intercellular coupling mechanisms, which confer robustness, stability and amplitude to the system. There has been remarkable progress to our understanding of the intra‐ and inter‐cellular mechanisms of the SCN circuitry over the last ~20 years, which has come hand‐in‐hand with the development of new technologies to measure and manipulate the clock.

European Journal of Neuroscience, EarlyView. Synchronization and maintenance of circadian timing in the mammalian clockwork doi:10.1111/ejn.14279 European Journal of Neuroscience 2018-12-05T11:33:32-08:00 European Journal of Neuroscience 10.1111/ejn.14279 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14279?af=R SPECIAL ISSUE REVIEW Circuit development in the master clock network of mammals Daily rhythms are generated by the circadian timekeeping system, which is orchestrated by the master circadian clock in the suprachiasmatic nucleus (SCN) of mammals. The SCN is a neural network of cellular clocks that interact with one another to determine the emergent properties of the system. Like other important neural circuits, the development of the SCN network is a gradual process that spans both embryonic and postnatal ages. This review discusses SCN development at the cellular and circuit levels, with a focus on work performed in model rodent species (i.e., mouse, rat, and hamster). Particular emphasis is placed on the spatial and temporal patterns of SCN development that may contribute to clock function in adulthood. Abstract Daily rhythms are generated by the circadian timekeeping system, which is orchestrated by the master circadian clock in the suprachiasmatic nucleus (SCN) of mammals. Circadian timekeeping is endogenous and does not require exposure to external cues during development. Nevertheless, the circadian system is not fully formed at birth in many mammalian species and it is important to understand how SCN development can affect the function of the circadian system in adulthood. The purpose of the current review is to discuss the ontogeny of cellular and circuit function in the SCN, with a focus on work performed in model rodent species (i.e., mouse, rat, and hamster). Particular emphasis is placed on the spatial and temporal patterns of SCN development that may contribute to the function of the master clock during adulthood. Additional work aimed at decoding the mechanisms that guide circadian development is expected to provide a solid foundation upon which to better understand the sources and factors contributing to aberrant maturation of clock function. Vania Carmona‐Alcocer, Kayla E. Rohr, Deborah A. M. Joye, Jennifer A. Evans https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14259?af=R European Journal of Neuroscience Circuit development in the master clock network of mammals

Daily rhythms are generated by the circadian timekeeping system, which is orchestrated by the master circadian clock in the suprachiasmatic nucleus (SCN) of mammals. The SCN is a neural network of cellular clocks that interact with one another to determine the emergent properties of the system. Like other important neural circuits, the development of the SCN network is a gradual process that spans both embryonic and postnatal ages. This review discusses SCN development at the cellular and circuit levels, with a focus on work performed in model rodent species (i.e., mouse, rat, and hamster). Particular emphasis is placed on the spatial and temporal patterns of SCN development that may contribute to clock function in adulthood.

 

Abstract

Daily rhythms are generated by the circadian timekeeping system, which is orchestrated by the master circadian clock in the suprachiasmatic nucleus (SCN) of mammals. Circadian timekeeping is endogenous and does not require exposure to external cues during development. Nevertheless, the circadian system is not fully formed at birth in many mammalian species and it is important to understand how SCN development can affect the function of the circadian system in adulthood. The purpose of the current review is to discuss the ontogeny of cellular and circuit function in the SCN, with a focus on work performed in model rodent species (i.e., mouse, rat, and hamster). Particular emphasis is placed on the spatial and temporal patterns of SCN development that may contribute to the function of the master clock during adulthood. Additional work aimed at decoding the mechanisms that guide circadian development is expected to provide a solid foundation upon which to better understand the sources and factors contributing to aberrant maturation of clock function.

European Journal of Neuroscience, EarlyView. Circuit development in the master clock network of mammalsdoi:10.1111/ejn.14259European Journal of Neuroscience2018-12-05T10:48:47-08:00European Journal of Neuroscience10.1111/ejn.14259 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14259?af=RSPECIAL ISSUE REVIEWCircadian disruption: What do we actually mean? Abstract The circadian system regulates physiology and behavior. Acute challenges to the system, such as those experienced when traveling across time zones, will eventually result in re‐synchronization to local environmental time cues, but this re‐synchronization is oftentimes accompanied by adverse short‐term consequences. When such challenges are experienced chronically, adaptation may not be achieved, as for example in the case of rotating night shift workers. The transient and chronic disturbance of the circadian system is most frequently referred to as “circadian disruption”, but many other terms have been proposed and used to refer to similar situations. It is now beyond doubt that the circadian system contributes to health and disease, emphasizing the need for clear terminology when describing challenges to the circadian system and their consequences. The goal of this review is to provide an overview of the terms used to describe disruption of the circadian system, discuss proposed quantifications of disruption in experimental and observational settings with a focus on human research, and highlight limitations and challenges of currently available tools. For circadian research to advance as a translational science, clear, operationalizable, and scalable quantifications of circadian disruption are key, as they will enable improved assessment and reproducibility of results, ideally ranging from mechanistic settings, including animal research, to large‐scale randomized clinical trials. Céline Vetter https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14255?af=R

Abstract

The circadian system regulates physiology and behavior. Acute challenges to the system, such as those experienced when traveling across time zones, will eventually result in re‐synchronization to local environmental time cues, but this re‐synchronization is oftentimes accompanied by adverse short‐term consequences. When such challenges are experienced chronically, adaptation may not be achieved, as for example in the case of rotating night shift workers. The transient and chronic disturbance of the circadian system is most frequently referred to as “circadian disruption”, but many other terms have been proposed and used to refer to similar situations. It is now beyond doubt that the circadian system contributes to health and disease, emphasizing the need for clear terminology when describing challenges to the circadian system and their consequences. The goal of this review is to provide an overview of the terms used to describe disruption of the circadian system, discuss proposed quantifications of disruption in experimental and observational settings with a focus on human research, and highlight limitations and challenges of currently available tools. For circadian research to advance as a translational science, clear, operationalizable, and scalable quantifications of circadian disruption are key, as they will enable improved assessment and reproducibility of results, ideally ranging from mechanistic settings, including animal research, to large‐scale randomized clinical trials.

European Journal of Neuroscience, EarlyView.Circadian disruption: What do we actually mean?doi:10.1111/ejn.14255European Journal of Neuroscience2018-12-05T04:20:25-08:00European Journal of Neuroscience10.1111/ejn.14255 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14255?af=RSPECIAL ISSUE REVIEWThe prodromes of Parkinson's disease Abstract Whilst the diagnosis of Parkinson's disease (PD) relies on the motor triad of bradykinesia, rigidity and tremor, the underlying pathological process starts many years before these signs are overt. In this prodromal phase of PD, a diverse range of non‐motor and motor features can occur. Individually they do not allow a diagnosis of PD, but when considered together, they reflect the gradual development of the clinical syndrome. Different subgroups within the prodromal phase may exist and reflect different underlying pathology. Here, we summarise the evidence on the prodromal phase of PD in patient groups at increased risk of PD with well described prodromal features: patients with idiopathic rapid eye movement sleep behaviour disorder, patients with idiopathic anosmia and families with monogenic mutations that are closely linked to PD pathology. In addition, we discuss the information on prodromal features from ongoing studies aimed at detecting prodromal PD in the general population. It is likely that better delineation of the clinical prodromes of PD and their progression in these high‐risk groups will improve understanding of the underlying pathophysiology. Richard Nathaniel Rees, Alastair John Noyce, Anette Schrag https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14269?af=R

Abstract

Whilst the diagnosis of Parkinson's disease (PD) relies on the motor triad of bradykinesia, rigidity and tremor, the underlying pathological process starts many years before these signs are overt. In this prodromal phase of PD, a diverse range of non‐motor and motor features can occur. Individually they do not allow a diagnosis of PD, but when considered together, they reflect the gradual development of the clinical syndrome. Different subgroups within the prodromal phase may exist and reflect different underlying pathology. Here, we summarise the evidence on the prodromal phase of PD in patient groups at increased risk of PD with well described prodromal features: patients with idiopathic rapid eye movement sleep behaviour disorder, patients with idiopathic anosmia and families with monogenic mutations that are closely linked to PD pathology. In addition, we discuss the information on prodromal features from ongoing studies aimed at detecting prodromal PD in the general population. It is likely that better delineation of the clinical prodromes of PD and their progression in these high‐risk groups will improve understanding of the underlying pathophysiology.

European Journal of Neuroscience, EarlyView. The prodromes of Parkinson's disease doi:10.1111/ejn.14269 European Journal of Neuroscience 2018-12-05T04:13:18-08:00 European Journal of Neuroscience 10.1111/ejn.14269 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14269?af=R SPECIAL ISSUE ARTICLE Adaptive neurogenesis in the cerebral cortex and contralateral subventricular zone induced by unilateral cortical devascularization: Possible modulation by dopamine neurotransmission Cell proliferation was induced by Unilateral Cortical Devascularization in C57 BL/6 mice. Increased neurogenesis was demonstrated after multiple pulses of BrdU administration in the perilesional parenchymal cortex and in the ipsilateral, but more important in the contralateral subventricular and rostral migratory stream zones. A possible modulation of dopaminergic system was supported by higher vesicular monoamine transporter 2 expression in the contralateral subventricular zone. Abstract Understanding endogenous neurogenesis and neuronal replacement to mature circuits is a topic of discussion as a therapeutic alternative under acute and chronic neurodegenerative disorders. Adaptive neurogenic response may result as a result of ischemia which could support long‐term recovery of behavioral functions. Endogenous sources of neural progenitors may be stimulated by changes in blood flow or neuromodulation. Using a mouse model of unilateral cortical devascularization, we have observed reactive neurogenesis in the perilesional cortex and subventricular zone neurogenic niche. C57BL/6L 4 weeks old male mice were craneotomized at 1 mm caudal from frontal suture and 1 mm lateral from midline to generate a window of 3 mm side. Brain injury was produced by removal of the meninges and superficial vasculature of dorsal parietal cortex. BrdU agent (50 mg/kg, ip) was injected to lesioned and sham animals, during days 0 and 1 after surgery. Sagittal sections were analyzed at 1, 4, 7, and 10 days post‐injury. A time‐dependent increase in BrdU+ cells in the perilesional parietal cortex was accompanied by augmented BrdU+ cells in the sub ventricular and rostral migratory stream of ipsilateral and contralateral hemispheres. Neural progenitors and neuroblasts proliferated in the lesioned and non‐lesioned subventricular zone and rostral migratory stream on day 4 after injury. Augmented contralateral neurogenesis was associated with an increase in vesicular monoamine transporter 2 protein in the striosomal sub ventricular neurogenic niche of non‐lesioned hemisphere. Leslie Vargas‐Saturno, Carlos Ayala‐Grosso https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14260?af=R European Journal of Neuroscience Adaptive neurogenesis in the cerebral cortex and contralateral subventricular zone induced by unilateral cortical devascularization: Possible modulation by dopamine neurotransmission

Cell proliferation was induced by Unilateral Cortical Devascularization in C57 BL/6 mice. Increased neurogenesis was demonstrated after multiple pulses of BrdU administration in the perilesional parenchymal cortex and in the ipsilateral, but more important in the contralateral subventricular and rostral migratory stream zones. A possible modulation of dopaminergic system was supported by higher vesicular monoamine transporter 2 expression in the contralateral subventricular zone.

 

Abstract

Understanding endogenous neurogenesis and neuronal replacement to mature circuits is a topic of discussion as a therapeutic alternative under acute and chronic neurodegenerative disorders. Adaptive neurogenic response may result as a result of ischemia which could support long‐term recovery of behavioral functions. Endogenous sources of neural progenitors may be stimulated by changes in blood flow or neuromodulation. Using a mouse model of unilateral cortical devascularization, we have observed reactive neurogenesis in the perilesional cortex and subventricular zone neurogenic niche. C57BL/6L 4 weeks old male mice were craneotomized at 1 mm caudal from frontal suture and 1 mm lateral from midline to generate a window of 3 mm side. Brain injury was produced by removal of the meninges and superficial vasculature of dorsal parietal cortex. BrdU agent (50 mg/kg, ip) was injected to lesioned and sham animals, during days 0 and 1 after surgery. Sagittal sections were analyzed at 1, 4, 7, and 10 days post‐injury. A time‐dependent increase in BrdU+ cells in the perilesional parietal cortex was accompanied by augmented BrdU+ cells in the sub ventricular and rostral migratory stream of ipsilateral and contralateral hemispheres. Neural progenitors and neuroblasts proliferated in the lesioned and non‐lesioned subventricular zone and rostral migratory stream on day 4 after injury. Augmented contralateral neurogenesis was associated with an increase in vesicular monoamine transporter 2 protein in the striosomal sub ventricular neurogenic niche of non‐lesioned hemisphere.

European Journal of Neuroscience, Volume 48, Issue 12, Page 3514-3533, December 2018. Adaptive neurogenesis in the cerebral cortex and contralateral subventricular zone induced by unilateral cortical devascularization: Possible modulation by dopamine neurotransmission doi:10.1111/ejn.14260 European Journal of Neuroscience 2018-12-04T03:00:56-08:00 European Journal of Neuroscience 48 12 2018-12-01T08:00:00Z 2018-12-01T08:00:00Z 10.1111/ejn.14260 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14260?af=R RESEARCH REPORT Interneuronal gap junctions increase synchrony and robustness of hippocampal ripple oscillations Hippocampal sharp wave–ripples are important for memory consolidation. Using simulations of CA1 recurrent interneuron networks, we show that interneuronal gap junctions support ripple oscillations (~200 Hz). Interneuronal gap junctions increase the synchrony of ripples beyond a level that can be achieved by increasing the strength of recurrent inhibition, reduce the network size necessary for the emergence of ripples, but have little effect on the oscillation frequency. Abstract Sharp wave–ripples (SWRs) are important for memory consolidation. Their signature in the hippocampal extracellular field potential can be decomposed into a ≈100 ms long sharp wave superimposed by ≈200 Hz ripple oscillations. How ripple oscillations are generated is currently not well understood. A promising model for the genesis of ripple oscillations is based on recurrent interneuronal networks (INT‐INT). According to this hypothesis, the INT‐INT network in CA1 receives a burst of excitation from CA3 that generates the sharp wave, and recurrent inhibition leads to an ultrafast synchronization of the CA1 network causing the ripple oscillations; fast‐spiking parvalbumin‐positive basket cells (PV+ BCs) may constitute the ripple‐generating interneuronal network. PV+ BCs are also coupled by gap junctions (GJs) but the function of GJs for ripple oscillations has not been quantified. Using simulations of CA1 hippocampal networks of PV+ BCs, we show that GJs promote synchrony beyond a level that could be obtained by only inhibition. GJs also increase the neuronal firing rate of the interneuronal ensemble, while they affect the ripple frequency only mildly. The promoting effect of GJs on ripple oscillations depends on fast GJ transmission (0.5 ms), which requires proximal GJ coupling (100 μm from soma), but is robust to variability in the delay and the amplitude of GJ coupling. André Holzbecher, Richard Kempter https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14267?af=R European Journal of Neuroscience Interneuronal gap junctions increase synchrony and robustness of hippocampal ripple oscillations

Hippocampal sharp wave–ripples are important for memory consolidation. Using simulations of CA1 recurrent interneuron networks, we show that interneuronal gap junctions support ripple oscillations (~200 Hz). Interneuronal gap junctions increase the synchrony of ripples beyond a level that can be achieved by increasing the strength of recurrent inhibition, reduce the network size necessary for the emergence of ripples, but have little effect on the oscillation frequency.

 

Abstract

Sharp wave–ripples (SWRs) are important for memory consolidation. Their signature in the hippocampal extracellular field potential can be decomposed into a ≈100 ms long sharp wave superimposed by ≈200 Hz ripple oscillations. How ripple oscillations are generated is currently not well understood. A promising model for the genesis of ripple oscillations is based on recurrent interneuronal networks (INT‐INT). According to this hypothesis, the INT‐INT network in CA1 receives a burst of excitation from CA3 that generates the sharp wave, and recurrent inhibition leads to an ultrafast synchronization of the CA1 network causing the ripple oscillations; fast‐spiking parvalbumin‐positive basket cells (PV+ BCs) may constitute the ripple‐generating interneuronal network. PV+ BCs are also coupled by gap junctions (GJs) but the function of GJs for ripple oscillations has not been quantified. Using simulations of CA1 hippocampal networks of PV+ BCs, we show that GJs promote synchrony beyond a level that could be obtained by only inhibition. GJs also increase the neuronal firing rate of the interneuronal ensemble, while they affect the ripple frequency only mildly. The promoting effect of GJs on ripple oscillations depends on fast GJ transmission (0.5 ms), which requires proximal GJ coupling (100 μm from soma), but is robust to variability in the delay and the amplitude of GJ coupling.

European Journal of Neuroscience, Volume 48, Issue 12, Page 3446-3465, December 2018. Interneuronal gap junctions increase synchrony and robustness of hippocampal ripple oscillationsdoi:10.1111/ejn.14267European Journal of Neuroscience2018-12-04T03:00:56-08:00European Journal of Neuroscience48122018-12-01T08:00:00Z2018-12-01T08:00:00Z10.1111/ejn.14267 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14267?af=RRESEARCH REPORT Pedunculopontine tegmentum cholinergic loss leads to a progressive decline in motor abilities and neuropathological changes resembling progressive supranuclear palsy Abstract Progressive supranuclear palsy (PSP) is the most common atypical Parkinsonism. Although PSP shares some symptomology with Parkinson's disease (PD), PSP has a different underlying pathology characterized by tau aggregation. Furthermore, PSP sufferers respond poorly to PD medications and there are no effective alternative therapeutics. The development of both palliative and disease altering therapeutics has been hampered by the lack of an animal model that displays relevant PSP‐like pathology and behavioral deficits. Previously, our lab found that in rats the selective removal of cholinergic pedunculopontine neurons (whose axonal projections overlap with areas of PSP pathology), mimics the extensive loss of cholinergic pedunculopontine neurons seen in PSP, and produces a unique PSP‐like combination of deficits in: startle reflex, attention, and motor function. The present study extends those findings by allowing the lesion to incubate for over a year and compares behavioral and post‐mortem pathology of pedunculopontine‐cholinergic‐lesioned and sham‐lesioned rats. There was an early startle reflex deficit which did not improve over time. Progressive declines in motor function developed over the course of the year, including an increase in the number of “slips” while navigating various beams and poorly coordinated transitions from an elevated platform into homecages. Histological analysis discovered that the loss off cholinergic pedunculopontine neurons precipitated a significant loss of substantia nigra tyrosine hydroxylase‐positive neurons and a significant enlargement of the lateral ventricles. The latter is a distinguishing feature between PSP and PD. This preclinical animal model of PSP has the potential to further our understanding of PSP and aid in the testing of potential therapeutic agents. Duncan A.A. MacLaren, Trisha L. Ljungberg, Meghan E. Griffin, Stewart D. Clark https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14212?af=R

Abstract

Progressive supranuclear palsy (PSP) is the most common atypical Parkinsonism. Although PSP shares some symptomology with Parkinson's disease (PD), PSP has a different underlying pathology characterized by tau aggregation. Furthermore, PSP sufferers respond poorly to PD medications and there are no effective alternative therapeutics. The development of both palliative and disease altering therapeutics has been hampered by the lack of an animal model that displays relevant PSP‐like pathology and behavioral deficits. Previously, our lab found that in rats the selective removal of cholinergic pedunculopontine neurons (whose axonal projections overlap with areas of PSP pathology), mimics the extensive loss of cholinergic pedunculopontine neurons seen in PSP, and produces a unique PSP‐like combination of deficits in: startle reflex, attention, and motor function. The present study extends those findings by allowing the lesion to incubate for over a year and compares behavioral and post‐mortem pathology of pedunculopontine‐cholinergic‐lesioned and sham‐lesioned rats. There was an early startle reflex deficit which did not improve over time. Progressive declines in motor function developed over the course of the year, including an increase in the number of “slips” while navigating various beams and poorly coordinated transitions from an elevated platform into homecages. Histological analysis discovered that the loss off cholinergic pedunculopontine neurons precipitated a significant loss of substantia nigra tyrosine hydroxylase‐positive neurons and a significant enlargement of the lateral ventricles. The latter is a distinguishing feature between PSP and PD. This preclinical animal model of PSP has the potential to further our understanding of PSP and aid in the testing of potential therapeutic agents.

European Journal of Neuroscience, Volume 48, Issue 12, Page 3477-3497, December 2018. Pedunculopontine tegmentum cholinergic loss leads to a progressive decline in motor abilities and neuropathological changes resembling progressive supranuclear palsy doi:10.1111/ejn.14212 European Journal of Neuroscience 2018-12-04T03:00:56-08:00 European Journal of Neuroscience 48 12 2018-12-01T08:00:00Z 2018-12-01T08:00:00Z 10.1111/ejn.14212 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14212?af=R RESEARCH REPORT Difference in the generalization of response tolerance across views between the anterior and posterior part of the inferotemporal cortex After discrimination experience of object images within the same viewing angles, neurons in area TE, which is the final stage of the ventral visual stream where object information are processed, demonstrate viewing angle tolerance to nearby views of the experienced objects, while neurons in area TEO which supply main visual inputs to area TE did not. Our results suggest the viewing angle tolerance may be a property generated in area TE and not in the earlier stages in the ventral visual pathway. Abstract The inferotemporal cortex consists of an anterior (cytoarchitectonic area TE) and a posterior (area TEO) part, which together constitute the final areas of the ventral visual stream, which is critical for object discrimination. Area TE receives dense projections from area TEO. We have previously identified a response tolerance in the cells in area TE in monkeys to a range of viewing angles after object discrimination at each of several views. To investigate the contribution of area TEO to the establishment of such a response tolerance in area TE, we conducted electrophysiological recordings of the responses of the single cells in area TEO after performance saturation of object discrimination at several independent views, without any association across views, and compared them with those obtained from the TE cells. The cells in area TEO showed responses to the experienced object views, but not to nearby views. Comparisons of the tunings of the TE and TEO cells to different viewing angles for the same object sets in the same animal showed that cells in area TEO had a significantly narrower tuning width, whereas the response tolerance was usually observed in the TE cells across viewing angles up to 60°. Our findings revealed a significant difference in the representation of the object views between areas TE and TEO, and suggested that such a representation in area TE may be completed through neuronal mechanisms within area TE, which is not a property of the earlier stages of the ventral visual stream. Jun‐ya Okamura, Koki Uemura, Shintaro Saruwatari, Gang Wang https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14162?af=R European Journal of Neuroscience Difference in the generalization of response tolerance across views between the anterior and posterior part of the inferotemporal cortex

After discrimination experience of object images within the same viewing angles, neurons in area TE, which is the final stage of the ventral visual stream where object information are processed, demonstrate viewing angle tolerance to nearby views of the experienced objects, while neurons in area TEO which supply main visual inputs to area TE did not. Our results suggest the viewing angle tolerance may be a property generated in area TE and not in the earlier stages in the ventral visual pathway.

 

Abstract

The inferotemporal cortex consists of an anterior (cytoarchitectonic area TE) and a posterior (area TEO) part, which together constitute the final areas of the ventral visual stream, which is critical for object discrimination. Area TE receives dense projections from area TEO. We have previously identified a response tolerance in the cells in area TE in monkeys to a range of viewing angles after object discrimination at each of several views. To investigate the contribution of area TEO to the establishment of such a response tolerance in area TE, we conducted electrophysiological recordings of the responses of the single cells in area TEO after performance saturation of object discrimination at several independent views, without any association across views, and compared them with those obtained from the TE cells. The cells in area TEO showed responses to the experienced object views, but not to nearby views. Comparisons of the tunings of the TE and TEO cells to different viewing angles for the same object sets in the same animal showed that cells in area TEO had a significantly narrower tuning width, whereas the response tolerance was usually observed in the TE cells across viewing angles up to 60°. Our findings revealed a significant difference in the representation of the object views between areas TE and TEO, and suggested that such a representation in area TE may be completed through neuronal mechanisms within area TE, which is not a property of the earlier stages of the ventral visual stream.

European Journal of Neuroscience, Volume 48, Issue 12, Page 3552-3566, December 2018. Difference in the generalization of response tolerance across views between the anterior and posterior part of the inferotemporal cortex doi:10.1111/ejn.14162 European Journal of Neuroscience 2018-12-04T03:00:56-08:00 European Journal of Neuroscience 48 12 2018-12-01T08:00:00Z 2018-12-01T08:00:00Z 10.1111/ejn.14162 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14162?af=R RESEARCH REPORT Human posterior parietal cortex responds to visual stimuli as early as peristriate occipital cortex Visual onset latencies in retinotopically mapped regions of the human posterior cortex were estimated from intracranial recordings. The spatiotemporal progression of response onsets broadly reflected the known hierarchy of visual areas with a clear exception—a robust and early onset at the intraparietal sulcus, responding nearly simultaneously with striate and peristriate areas. Abstract Much of what is known about the timing of visual processing in the brain is inferred from intracranial studies in monkeys, with human data limited to mainly noninvasive methods with lower spatial resolution. Here, we estimated visual onset latencies from electrocorticographic (ECoG) recordings in a patient who was implanted with 112 subdural electrodes, distributed across the posterior cortex of the right hemisphere, for presurgical evaluation of intractable epilepsy. Functional MRI prior to surgery was used to determine boundaries of visual areas. The patient was presented with images of objects from several categories. Event‐related potentials (ERPs) were calculated across all categories excluding targets, and statistically reliable onset latencies were determined, using a bootstrapping procedure over the single trial baseline activity in individual electrodes. The distribution of onset latencies broadly reflected the known hierarchy of visual areas, with the earliest cortical responses in primary visual cortex, and higher areas showing later responses. A clear exception to this pattern was a robust, statistically reliable and spatially localized, very early response, on the bank of the posterior intraparietal sulcus (IPS). The response in the IPS started nearly simultaneously with responses detected in peristriate visual areas, around 60 ms poststimulus onset. Our results support the notion of early visual processing in the posterior parietal lobe, not respecting traditional hierarchies, and give direct evidence for onset times of visual responses across the human cortex. Tamar I. Regev, Jonathan Winawer, Edden M. Gerber, Robert T. Knight, Leon Y. Deouell https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14164?af=R European Journal of Neuroscience Human posterior parietal cortex responds to visual stimuli as early as peristriate occipital cortex

Visual onset latencies in retinotopically mapped regions of the human posterior cortex were estimated from intracranial recordings. The spatiotemporal progression of response onsets broadly reflected the known hierarchy of visual areas with a clear exception—a robust and early onset at the intraparietal sulcus, responding nearly simultaneously with striate and peristriate areas.

 

Abstract

Much of what is known about the timing of visual processing in the brain is inferred from intracranial studies in monkeys, with human data limited to mainly noninvasive methods with lower spatial resolution. Here, we estimated visual onset latencies from electrocorticographic (ECoG) recordings in a patient who was implanted with 112 subdural electrodes, distributed across the posterior cortex of the right hemisphere, for presurgical evaluation of intractable epilepsy. Functional MRI prior to surgery was used to determine boundaries of visual areas. The patient was presented with images of objects from several categories. Event‐related potentials (ERPs) were calculated across all categories excluding targets, and statistically reliable onset latencies were determined, using a bootstrapping procedure over the single trial baseline activity in individual electrodes. The distribution of onset latencies broadly reflected the known hierarchy of visual areas, with the earliest cortical responses in primary visual cortex, and higher areas showing later responses. A clear exception to this pattern was a robust, statistically reliable and spatially localized, very early response, on the bank of the posterior intraparietal sulcus (IPS). The response in the IPS started nearly simultaneously with responses detected in peristriate visual areas, around 60 ms poststimulus onset. Our results support the notion of early visual processing in the posterior parietal lobe, not respecting traditional hierarchies, and give direct evidence for onset times of visual responses across the human cortex.

European Journal of Neuroscience, Volume 48, Issue 12, Page 3567-3582, December 2018. Human posterior parietal cortex responds to visual stimuli as early as peristriate occipital cortex doi:10.1111/ejn.14164 European Journal of Neuroscience 2018-12-04T03:00:56-08:00 European Journal of Neuroscience 48 12 2018-12-01T08:00:00Z 2018-12-01T08:00:00Z 10.1111/ejn.14164 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14164?af=R RESEARCH REPORT Synchrony surfacing: Epicortical recording of correlated action potentials We have compared spiking activity in simultaneous recordings from layers and the intact surface (ECoG) of sensory cortices in the ferret brain. Surface spiking reflected the truly representative activity of the cortical column, i.e. spikes fired in synchrony by several units. We show that this can sharpen tuning, reduce response variability and thus make single trial surface spiking data as informative as post hoc analyzed multi trial or population data from intracortical multi site recordings. Abstract Synchronous spiking of multiple neurons is a key phenomenon in normal brain function and pathologies. Recently, approaches to record spikes from the intact cortical surface using small high‐density arrays of microelectrodes have been reported. It remained unaddressed how epicortical spiking relates to intracortical unit activity. We introduced a mesoscale approach using an array of 64 electrodes with intermediate diameter (250 μm) and combined large‐coverage epicortical recordings in ferrets with intracortical recordings via laminar probes. Empirical data and modelling strongly suggest that our epicortical electrodes selectively captured synchronized spiking of neurons in the cortex beneath. As a result, responses to sensory stimulation were more robust and less noisy compared to intracortical activity, and receptive field properties were well preserved in epicortical recordings. This should promote insights into assembly‐coding beyond the informative value of subdural EEG or single‐unit spiking, and be advantageous to real‐time applications in brain‐machine interfacing. Tobias Bockhorst, Florian Pieper, Gerhard Engler, Thomas Stieglitz, Edgar Galindo‐Leon, Andreas K. Engel https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14167?af=R European Journal of Neuroscience Synchrony surfacing: Epicortical recording of correlated action potentials

We have compared spiking activity in simultaneous recordings from layers and the intact surface (ECoG) of sensory cortices in the ferret brain. Surface spiking reflected the truly representative activity of the cortical column, i.e. spikes fired in synchrony by several units. We show that this can sharpen tuning, reduce response variability and thus make single trial surface spiking data as informative as post hoc analyzed multi trial or population data from intracortical multi site recordings.

 

Abstract

Synchronous spiking of multiple neurons is a key phenomenon in normal brain function and pathologies. Recently, approaches to record spikes from the intact cortical surface using small high‐density arrays of microelectrodes have been reported. It remained unaddressed how epicortical spiking relates to intracortical unit activity. We introduced a mesoscale approach using an array of 64 electrodes with intermediate diameter (250 μm) and combined large‐coverage epicortical recordings in ferrets with intracortical recordings via laminar probes. Empirical data and modelling strongly suggest that our epicortical electrodes selectively captured synchronized spiking of neurons in the cortex beneath. As a result, responses to sensory stimulation were more robust and less noisy compared to intracortical activity, and receptive field properties were well preserved in epicortical recordings. This should promote insights into assembly‐coding beyond the informative value of subdural EEG or single‐unit spiking, and be advantageous to real‐time applications in brain‐machine interfacing.

European Journal of Neuroscience, Volume 48, Issue 12, Page 3583-3596, December 2018. Synchrony surfacing: Epicortical recording of correlated action potentials doi:10.1111/ejn.14167 European Journal of Neuroscience 2018-12-04T03:00:56-08:00 European Journal of Neuroscience 48 12 2018-12-01T08:00:00Z 2018-12-01T08:00:00Z 10.1111/ejn.14167 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14167?af=R RESEARCH REPORT Survivin overexpression via adeno‐associated virus vector Rh10 ameliorates ischemic damage after middle cerebral artery occlusion in rats Rats were injected with 4×109 vg of adeno‐associated virus (AAV)‐green fluorescent protein (GFP) or AAV‐His‐survivin into the right striatum and were treated three weeks later with transient middle cerebral artery occlusion (MCAO) for 90 minutes. Twenty‐four hours after MCAO, functional analysis did not show significant difference. Histological analyses showed that AAV‐His‐survivin treatment significantly reduced the infarction volume and decreased apoptotic markers in the ischemic boundary zone, but not the neutrophil infiltration. Abstract Survivin, a member of the inhibitors of apoptosis protein gene family, inhibits the activity of caspase, leading to a halt of the apoptotic process. Our study focused on the neuroprotective effect of survivin after transient middle cerebral artery occlusion (MCAO) with intraparenchymal administration of an adeno‐associated virus (AAV) vector. His‐tagged survivin was cloned and packaged into the AAV‐rh10 vector. Four‐week‐old Sprague–Dawley rats were injected with 4 × 109 vg of AAV‐GFP or AAV‐His‐survivin into the right striatum and were treated 3 weeks later with transient MCAO for 90 min. Twenty‐four hours after MCAO, functional and histological analyses of the rats were performed. The result showed that rats that had been treated with AAV‐green fluorescent protein (GFP) and those that had been treated with AAV‐His‐survivin did not show a significant difference in neurological scores 24 hr after MCAO, however, infarction volume was significantly reduced in the AAV‐His‐survivin group compared to that in the AAV‐GFP group. Although the neutrophil marker myeloperoxidase did not show a significant difference in the ischemic boundary zone, cells positive for active caspase‐3 and terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick end labeling were significantly decreased in the AAV‐His‐survivin group. In conclusion, survivin overexpression in the ischemic boundary zone induced by using an AAV vector has the potential for amelioration of ischemic damage via an antiapoptotic mechanism. Yoshihide Sehara, Toshiki Inaba, Takao Urabe, Fumio Kurosaki, Masashi Urabe, Naoki Kaneko, Kuniko Shimazaki, Kensuke Kawai, Hiroaki Mizukami https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14169?af=R European Journal of Neuroscience Survivin overexpression via adeno‐associated virus vector Rh10 ameliorates ischemic damage after middle cerebral artery occlusion in rats

Rats were injected with 4×109 vg of adeno‐associated virus (AAV)‐green fluorescent protein (GFP) or AAV‐His‐survivin into the right striatum and were treated three weeks later with transient middle cerebral artery occlusion (MCAO) for 90 minutes. Twenty‐four hours after MCAO, functional analysis did not show significant difference. Histological analyses showed that AAV‐His‐survivin treatment significantly reduced the infarction volume and decreased apoptotic markers in the ischemic boundary zone, but not the neutrophil infiltration.

 

Abstract

Survivin, a member of the inhibitors of apoptosis protein gene family, inhibits the activity of caspase, leading to a halt of the apoptotic process. Our study focused on the neuroprotective effect of survivin after transient middle cerebral artery occlusion (MCAO) with intraparenchymal administration of an adeno‐associated virus (AAV) vector. His‐tagged survivin was cloned and packaged into the AAV‐rh10 vector. Four‐week‐old Sprague–Dawley rats were injected with 4 × 109 vg of AAV‐GFP or AAV‐His‐survivin into the right striatum and were treated 3 weeks later with transient MCAO for 90 min. Twenty‐four hours after MCAO, functional and histological analyses of the rats were performed. The result showed that rats that had been treated with AAV‐green fluorescent protein (GFP) and those that had been treated with AAV‐His‐survivin did not show a significant difference in neurological scores 24 hr after MCAO, however, infarction volume was significantly reduced in the AAV‐His‐survivin group compared to that in the AAV‐GFP group. Although the neutrophil marker myeloperoxidase did not show a significant difference in the ischemic boundary zone, cells positive for active caspase‐3 and terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick end labeling were significantly decreased in the AAV‐His‐survivin group. In conclusion, survivin overexpression in the ischemic boundary zone induced by using an AAV vector has the potential for amelioration of ischemic damage via an antiapoptotic mechanism.

European Journal of Neuroscience, Volume 48, Issue 12, Page 3466-3476, December 2018. Survivin overexpression via adeno‐associated virus vector Rh10 ameliorates ischemic damage after middle cerebral artery occlusion in rats doi:10.1111/ejn.14169 European Journal of Neuroscience 2018-12-04T03:00:56-08:00 European Journal of Neuroscience 48 12 2018-12-01T08:00:00Z 2018-12-01T08:00:00Z 10.1111/ejn.14169 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14169?af=R RESEARCH REPORT Investigation of the changes in oscillatory power during task switching after mild traumatic brain injury Our project examines how multiple concussions, or mild traumatic brain injuries (mTBI), impact brain oscillations during a task‐switching paradigm. Multiple mTBIs lead to an overall decrease in task‐switching performance revealed through a decrease in switch and maintain trial accuracy combined. The changes in task performance may be related to differences in theta, alpha, and beta desynchronization over posterior brain regions. Abstract Mild traumatic brain injury (mTBI) can cause persistent cognitive changes. These cognitive changes may be due to changes in neural communication. Task‐switching is a cognitive control operation that may be susceptible to mTBI and is associated with oscillations in theta (4–7 Hz), alpha (8–13 Hz), and beta (14–30 Hz) ranges. This study aimed to investigate oscillatory power in response to cues indicating a task‐switch after mTBI. Electroencephalogram and behavioral data were collected from 21 participants with a history of two or more concussions (mTBI) and 21 age‐ and gender‐matched controls as they performed a task‐switching paradigm. Participants differentiated whether visual stimuli were red or green, or circles or squares, depending on a cue. The cue changed every few trials with the first trial after a rule change being termed a switch trial. The mTBI group showed significantly less overall accuracy during the task. Over a posterior parietal region, the mTBI group showed more theta desynchronization than the control group from ~300 to ~600 ms post‐cue during switch trials and from ~300 to 400 ms during maintain trials, along with less alpha and beta desynchronization than the control group from ~2,000 to ~2,200 ms post‐cue. In a right parietal region, the mTBI group showed less alpha and beta desynchronization from ~525 to ~775 ms post‐cue. However, there was no condition × group interaction in the behavior or oscillatory results. These oscillatory differences suggest a change in neural communication is present after mTBI that may relate to global changes in task performance. Stephanie E. Barlow, Paolo Medrano, Daniel R. Seichepine, Robert S. Ross https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14231?af=R European Journal of Neuroscience Investigation of the changes in oscillatory power during task switching after mild traumatic brain injury

Our project examines how multiple concussions, or mild traumatic brain injuries (mTBI), impact brain oscillations during a task‐switching paradigm. Multiple mTBIs lead to an overall decrease in task‐switching performance revealed through a decrease in switch and maintain trial accuracy combined. The changes in task performance may be related to differences in theta, alpha, and beta desynchronization over posterior brain regions.

 

Abstract

Mild traumatic brain injury (mTBI) can cause persistent cognitive changes. These cognitive changes may be due to changes in neural communication. Task‐switching is a cognitive control operation that may be susceptible to mTBI and is associated with oscillations in theta (4–7 Hz), alpha (8–13 Hz), and beta (14–30 Hz) ranges. This study aimed to investigate oscillatory power in response to cues indicating a task‐switch after mTBI. Electroencephalogram and behavioral data were collected from 21 participants with a history of two or more concussions (mTBI) and 21 age‐ and gender‐matched controls as they performed a task‐switching paradigm. Participants differentiated whether visual stimuli were red or green, or circles or squares, depending on a cue. The cue changed every few trials with the first trial after a rule change being termed a switch trial. The mTBI group showed significantly less overall accuracy during the task. Over a posterior parietal region, the mTBI group showed more theta desynchronization than the control group from ~300 to ~600 ms post‐cue during switch trials and from ~300 to 400 ms during maintain trials, along with less alpha and beta desynchronization than the control group from ~2,000 to ~2,200 ms post‐cue. In a right parietal region, the mTBI group showed less alpha and beta desynchronization from ~525 to ~775 ms post‐cue. However, there was no condition × group interaction in the behavior or oscillatory results. These oscillatory differences suggest a change in neural communication is present after mTBI that may relate to global changes in task performance.

European Journal of Neuroscience, Volume 48, Issue 12, Page 3498-3513, December 2018. Investigation of the changes in oscillatory power during task switching after mild traumatic brain injury doi:10.1111/ejn.14231 European Journal of Neuroscience 2018-12-04T03:00:56-08:00 European Journal of Neuroscience 48 12 2018-12-01T08:00:00Z 2018-12-01T08:00:00Z 10.1111/ejn.14231 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14231?af=R RESEARCH REPORT Suppression of somatosensory stimuli during motor planning may explain levels of balance and mobility after stroke Individuals with stroke did not show attention‐mediated gating of the N40 component associated with irrelevant somatosensory information during motor planning. It may be that dysfunction in pathways connecting to area 3b explains the lack of attention‐mediated gating of the N40. Attention‐mediated gating during motor planning explained significant and unique variance in a measure of community balance and mobility combined with response time. Abstract The ability to actively suppress, or gate, irrelevant sensory information is required for safe and efficient walking in sensory‐rich environments. Both motor attention and motor planning alter somatosensory evoked potentials (SEPs) in healthy adults. This study's aim was to examine the effect of motor attention on processing of irrelevant somatosensory information during plantar flexion motor planning after stroke. Thirteen healthy older adults and 11 individuals with stroke participated. Irrelevant tibial nerve stimulation was delivered while SEPs were recorded over Cz, overlaying the leg portion of the sensorimotor cortex at the vertex of the head. Three conditions were tested in both legs: (1) Rest, (2) Attend To, and (3) Attend Away from the stimulated limb. In conditions 2 and 3, relevant vibration cued voluntary plantar flexion movements of the stimulated (Attend To) or non‐stimulated (Attend Away) leg. SEP amplitudes were averaged during motor planning per condition. Individuals with stroke did not show attention‐mediated gating of the N40 component associated with irrelevant somatosensory information during motor planning. It may be that dysfunction in pathways connecting to area 3b explains the lack of attention‐mediated gating of the N40. Also, attention‐mediated gating during motor planning explained significant and unique variance in a measure of community balance and mobility combined with response time. Thus, the ability to gate irrelevant somatosensory information appears important for stepping in both older adults and after stroke. Our data suggest that therapies that direct motor attention could positively impact walking after stroke. Sue Peters, Katlyn E. Brown, S. Jayne Garland, W. Richard Staines, Todd C. Handy, Lara A. Boyd https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14136?af=R European Journal of Neuroscience Suppression of somatosensory stimuli during motor planning may explain levels of balance and mobility after stroke

Individuals with stroke did not show attention‐mediated gating of the N40 component associated with irrelevant somatosensory information during motor planning. It may be that dysfunction in pathways connecting to area 3b explains the lack of attention‐mediated gating of the N40. Attention‐mediated gating during motor planning explained significant and unique variance in a measure of community balance and mobility combined with response time.

 

Abstract

The ability to actively suppress, or gate, irrelevant sensory information is required for safe and efficient walking in sensory‐rich environments. Both motor attention and motor planning alter somatosensory evoked potentials (SEPs) in healthy adults. This study's aim was to examine the effect of motor attention on processing of irrelevant somatosensory information during plantar flexion motor planning after stroke. Thirteen healthy older adults and 11 individuals with stroke participated. Irrelevant tibial nerve stimulation was delivered while SEPs were recorded over Cz, overlaying the leg portion of the sensorimotor cortex at the vertex of the head. Three conditions were tested in both legs: (1) Rest, (2) Attend To, and (3) Attend Away from the stimulated limb. In conditions 2 and 3, relevant vibration cued voluntary plantar flexion movements of the stimulated (Attend To) or non‐stimulated (Attend Away) leg. SEP amplitudes were averaged during motor planning per condition. Individuals with stroke did not show attention‐mediated gating of the N40 component associated with irrelevant somatosensory information during motor planning. It may be that dysfunction in pathways connecting to area 3b explains the lack of attention‐mediated gating of the N40. Also, attention‐mediated gating during motor planning explained significant and unique variance in a measure of community balance and mobility combined with response time. Thus, the ability to gate irrelevant somatosensory information appears important for stepping in both older adults and after stroke. Our data suggest that therapies that direct motor attention could positively impact walking after stroke.

European Journal of Neuroscience, Volume 48, Issue 12, Page 3534-3551, December 2018. Suppression of somatosensory stimuli during motor planning may explain levels of balance and mobility after strokedoi:10.1111/ejn.14136European Journal of Neuroscience2018-12-04T03:00:56-08:00European Journal of Neuroscience48122018-12-01T08:00:00Z2018-12-01T08:00:00Z10.1111/ejn.14136 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14136?af=RRESEARCH REPORTIssue Information https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.13687?af=R European Journal of Neuroscience, Volume 48, Issue 12, Page i-iii, December 2018.Issue Informationdoi:10.1111/ejn.13687European Journal of Neuroscience2018-12-04T03:00:56-08:00European Journal of Neuroscience48122018-12-01T08:00:00Z2018-12-01T08:00:00Z10.1111/ejn.13687 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.13687?af=RISSUE INFORMATION Deterministic fate assignment of Müller glia cells in the zebrafish retina suggests a clonal backbone during development Abstract The optic cup houses multipotent retinal progenitor cells that proliferate and differentiate to form the mature retina, containing five main types of neurons and a single glial cell type, the Müller cell. Progenitors of the zebrafish optic cup generate clones that vary regarding the number and types of neurons, a process we previously showed could be described by stochastic models. Here, we present data indicating that each retinal progenitor cell, in the 24 hrs post‐fertilization optic cup, is predestined to form a single Müller cell. This striking fate assignment of Müller cells reveals a dual nature of retinal lineages where stochastic mechanisms produce variable numbers of neurons while there is a strong deterministic component governing the formation of glia cells. A possible mechanism for this stereotypic fate assignment could be the maintenance of a clonal backbone during retina development, which would be similar to invertebrate and rodent cortical neurogenesis. Steffen Rulands, Ana Belen Iglesias‐Gonzalez, Henrik Boije https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14257?af=R

Abstract

The optic cup houses multipotent retinal progenitor cells that proliferate and differentiate to form the mature retina, containing five main types of neurons and a single glial cell type, the Müller cell. Progenitors of the zebrafish optic cup generate clones that vary regarding the number and types of neurons, a process we previously showed could be described by stochastic models. Here, we present data indicating that each retinal progenitor cell, in the 24 hrs post‐fertilization optic cup, is predestined to form a single Müller cell. This striking fate assignment of Müller cells reveals a dual nature of retinal lineages where stochastic mechanisms produce variable numbers of neurons while there is a strong deterministic component governing the formation of glia cells. A possible mechanism for this stereotypic fate assignment could be the maintenance of a clonal backbone during retina development, which would be similar to invertebrate and rodent cortical neurogenesis.

European Journal of Neuroscience, Volume 48, Issue 12, Page 3597-3605, December 2018. Deterministic fate assignment of Müller glia cells in the zebrafish retina suggests a clonal backbone during development doi:10.1111/ejn.14257 European Journal of Neuroscience 2018-12-04T03:00:56-08:00 European Journal of Neuroscience 48 12 2018-12-01T08:00:00Z 2018-12-01T08:00:00Z 10.1111/ejn.14257 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14257?af=R SHORT COMMUNICATION Thalamic afferents to prefrontal cortices from ventral motor nuclei in decision‐making Here we review evidence that considers prefrontal cortex, basal ganglia, motor ventral thalamus (particularly, the ventromedial and ventral anterior nuclei) and their projection back to the prefrontal cortex, layer 1, as an important network involved in the learning of beneficial versus costly choices in the mouse. Abstract The focus of this literature review is on the three interacting brain areas that participate in decision‐making: basal ganglia, ventral motor thalamic nuclei, and medial prefrontal cortex, with an emphasis on the participation of the ventromedial and ventral anterior motor thalamic nuclei in prefrontal cortical function. Apart from a defining input from the mediodorsal thalamus, the prefrontal cortex receives inputs from ventral motor thalamic nuclei that combine to mediate typical prefrontal functions such as associative learning, action selection, and decision‐making. Motor, somatosensory and medial prefrontal cortices are mainly contacted in layer 1 by the ventral motor thalamic nuclei and in layer 3 by thalamocortical input from mediodorsal thalamus. We will review anatomical, electrophysiological, and behavioral evidence for the proposed participation of ventral motor thalamic nuclei and medial prefrontal cortex in rat and mouse motor decision‐making. Bianca Sieveritz, Marianela García‐Muñoz, Gordon W. Arbuthnott https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14215?af=R European Journal of Neuroscience Thalamic afferents to prefrontal cortices from ventral motor nuclei in decision‐making

Here we review evidence that considers prefrontal cortex, basal ganglia, motor ventral thalamus (particularly, the ventromedial and ventral anterior nuclei) and their projection back to the prefrontal cortex, layer 1, as an important network involved in the learning of beneficial versus costly choices in the mouse.

 

Abstract

The focus of this literature review is on the three interacting brain areas that participate in decision‐making: basal ganglia, ventral motor thalamic nuclei, and medial prefrontal cortex, with an emphasis on the participation of the ventromedial and ventral anterior motor thalamic nuclei in prefrontal cortical function. Apart from a defining input from the mediodorsal thalamus, the prefrontal cortex receives inputs from ventral motor thalamic nuclei that combine to mediate typical prefrontal functions such as associative learning, action selection, and decision‐making. Motor, somatosensory and medial prefrontal cortices are mainly contacted in layer 1 by the ventral motor thalamic nuclei and in layer 3 by thalamocortical input from mediodorsal thalamus. We will review anatomical, electrophysiological, and behavioral evidence for the proposed participation of ventral motor thalamic nuclei and medial prefrontal cortex in rat and mouse motor decision‐making.

European Journal of Neuroscience, EarlyView. Thalamic afferents to prefrontal cortices from ventral motor nuclei in decision‐making doi:10.1111/ejn.14215 European Journal of Neuroscience 2018-12-03T10:24:16-08:00 European Journal of Neuroscience 10.1111/ejn.14215 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14215?af=R Special Issue Review Rhythmic auditory cues shape neural network recruitment in Parkinson's disease during repetitive motor behavior Greater inter‐network correlations during motor tapping in a Rhythmic Auditory Stimulation paradigm in subjects with Parkinson's disease compared with controls. Abstract It is well established clinically that rhythmic auditory cues can improve gait and other motor behaviors in Parkinson's disease (PD) and other disorders. However, the neural systems underlying this therapeutic effect are largely unknown. To investigate this question we scanned people with PD and age‐matched healthy controls using functional magnetic resonance imaging (fMRI). All subjects performed a rhythmic motor behavior (right hand finger tapping) with and without simultaneous auditory rhythmic cues at two different speeds (1 and 4 Hz). We used spatial independent component analysis (ICA) and regression to identify task‐related functional connectivity networks and assessed differences between groups in intra‐ and inter‐network connectivity. Overall, the control group showed greater intra‐network connectivity in perceptual and motor related networks during motor tapping both with and without rhythmic cues. The PD group showed greater inter‐network connectivity between the auditory network and the executive control network, and between the executive control network and the motor/cerebellar network associated with the motor task performance. We interpret our results as indicating that the temporal rhythmic auditory information may assist compensatory mechanisms through network‐level effects, reflected in increased interaction between auditory and executive networks that in turn modulate activity in cortico‐cerebellar networks. Kurt Braunlich, Carol A. Seger, Kade G. Jentink, Isabelle Buard, Benzi M. Kluger, Michael H. Thaut https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14227?af=R European Journal of Neuroscience Rhythmic auditory cues shape neural network recruitment in Parkinson's disease during repetitive motor behavior

Greater inter‐network correlations during motor tapping in a Rhythmic Auditory Stimulation paradigm in subjects with Parkinson's disease compared with controls.

 

Abstract

It is well established clinically that rhythmic auditory cues can improve gait and other motor behaviors in Parkinson's disease (PD) and other disorders. However, the neural systems underlying this therapeutic effect are largely unknown. To investigate this question we scanned people with PD and age‐matched healthy controls using functional magnetic resonance imaging (fMRI). All subjects performed a rhythmic motor behavior (right hand finger tapping) with and without simultaneous auditory rhythmic cues at two different speeds (1 and 4 Hz). We used spatial independent component analysis (ICA) and regression to identify task‐related functional connectivity networks and assessed differences between groups in intra‐ and inter‐network connectivity. Overall, the control group showed greater intra‐network connectivity in perceptual and motor related networks during motor tapping both with and without rhythmic cues. The PD group showed greater inter‐network connectivity between the auditory network and the executive control network, and between the executive control network and the motor/cerebellar network associated with the motor task performance. We interpret our results as indicating that the temporal rhythmic auditory information may assist compensatory mechanisms through network‐level effects, reflected in increased interaction between auditory and executive networks that in turn modulate activity in cortico‐cerebellar networks.

European Journal of Neuroscience, EarlyView. Rhythmic auditory cues shape neural network recruitment in Parkinson's disease during repetitive motor behavior doi:10.1111/ejn.14227 European Journal of Neuroscience 2018-12-03T10:18:23-08:00 European Journal of Neuroscience 10.1111/ejn.14227 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14227?af=R Special Issue Article Meta‐analysis of aberrant post‐error slowing in substance use disorder: implications for behavioral adaptation and self‐control Substance use disorders are associated with poorer cognitive control, which in some studies has been indexed as reductions in post‐error slowing. However, due to inconsistencies within the literature, we undertook a meta‐analysis to reconcile existing findings. A random‐effects analysis revealed a moderate group difference across all studies (Cohen's d = 0.31), indicating diminished post‐error slowing in substance users; possibly contributing to impaired inhibitory control in this population. Abstract Individual with substance use disorders have well‐recognized impairments in cognitive control, including in behavioral adaptation after mistakes. One way in which this impairment manifests is via diminished post‐error slowing, the increase in reaction time following a task‐related error that is posited to reflect cautionary or corrective behavior. Yet, in the substance use disorder literature, findings with regard to post‐error slowing have been inconsistent, and thus could benefit from quantitative integration. Here, we conducted a meta‐analysis of case–control studies examining post‐error slowing in addiction. Twelve studies with 15 unique comparisons were identified, comprising 567 substance users and 384 healthy controls across three broad types of inhibitory control paradigms (go‐no/go, conflict resolution, and stop signal tasks, respectively). Results of the random‐effects meta‐analysis revealed a moderate group difference across all studies (Cohen's d = 0.31), such that the individuals with substance use disorder had diminished post‐error slowing compared with controls. Despite this omnibus effect, there was also large variability in the magnitude of the effects, explained in part by differences between studies in task complexity. These findings suggest that post‐error slowing may serve as a promising and easy‐to‐implement measure of cognitive control impairment in substance use disorder, with potential links to aberrant brain function in cognitive control areas such as the anterior cingulate cortex. Ryan M. Sullivan, Greg Perlman, Scott J. Moeller https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14229?af=R European Journal of Neuroscience Meta‐analysis of aberrant post‐error slowing in substance use disorder: implications for behavioral adaptation and self‐control

Substance use disorders are associated with poorer cognitive control, which in some studies has been indexed as reductions in post‐error slowing. However, due to inconsistencies within the literature, we undertook a meta‐analysis to reconcile existing findings. A random‐effects analysis revealed a moderate group difference across all studies (Cohen's d =0.31), indicating diminished post‐error slowing in substance users; possibly contributing to impaired inhibitory control in this population.

 

Abstract

Individual with substance use disorders have well‐recognized impairments in cognitive control, including in behavioral adaptation after mistakes. One way in which this impairment manifests is via diminished post‐error slowing, the increase in reaction time following a task‐related error that is posited to reflect cautionary or corrective behavior. Yet, in the substance use disorder literature, findings with regard to post‐error slowing have been inconsistent, and thus could benefit from quantitative integration. Here, we conducted a meta‐analysis of case–control studies examining post‐error slowing in addiction. Twelve studies with 15 unique comparisons were identified, comprising 567 substance users and 384 healthy controls across three broad types of inhibitory control paradigms (go‐no/go, conflict resolution, and stop signal tasks, respectively). Results of the random‐effects meta‐analysis revealed a moderate group difference across all studies (Cohen's d =0.31), such that the individuals with substance use disorder had diminished post‐error slowing compared with controls. Despite this omnibus effect, there was also large variability in the magnitude of the effects, explained in part by differences between studies in task complexity. These findings suggest that post‐error slowing may serve as a promising and easy‐to‐implement measure of cognitive control impairment in substance use disorder, with potential links to aberrant brain function in cognitive control areas such as the anterior cingulate cortex.

European Journal of Neuroscience, EarlyView. Meta‐analysis of aberrant post‐error slowing in substance use disorder: implications for behavioral adaptation and self‐control doi:10.1111/ejn.14229 European Journal of Neuroscience 2018-12-03T09:45:38-08:00 European Journal of Neuroscience 10.1111/ejn.14229 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14229?af=R Special Issue Review Modulating neural oscillations by transcranial static magnetic field stimulation of the dorsolateral prefrontal cortex: A crossover, double‐blind, sham‐controlled pilot study We applied transcranial static magnetic field stimulation to the dorsolateral prefrontal cortex and measured changes to neural oscillations. Contrary to prior findings of studies in the visual cortex, alpha power was unchanged at the site of stimulation, but we observed other alterations in the alpha, beta, and theta band. Our results indicate that the effect of transcranial static magnetic field stimulation on neural oscillations may be specific to the region stimulated. Abstract Transcranial static magnetic field stimulation (tSMS) is a novel non‐invasive brain stimulation technique that has been shown to locally increase alpha power in the parietal and occipital cortex. We investigated if tSMS locally increased alpha power in the left or right prefrontal cortex, as the balance of left/right prefrontal alpha power (frontal alpha asymmetry) has been linked to emotional processing and mood disorders. Therefore, altering frontal alpha asymmetry with tSMS may serve as a novel treatment to psychiatric diseases. We performed a crossover, double‐blind, sham‐controlled pilot study to assess the effects of prefrontal tSMS on neural oscillations. Twenty‐four right‐handed healthy participants were recruited and received left dorsolateral prefrontal cortex (DLPFC) tSMS, right DLPFC tSMS, and sham tSMS in a randomized order. Electroencephalography data were collected before (2 min eyes‐closed, 2 min eyes‐open), during (10 min eyes‐open), and after (2 min eyes‐open) stimulation. In contrast with our hypothesis, neither left nor right tSMS locally increased frontal alpha power. However, alpha power increased in occipital cortex during left DLPFC tSMS. Right DLPFC tSMS increased post‐stimulation fronto‐parietal theta power, indicating possible relevance to memory and cognition. Left and right DLPFC tSMS increased post‐stimulation left hemisphere beta power, indicating possible changes to motor behavior. Left DLPFC tSMS also increased post‐stimulation right frontal beta power, demonstrating complex network effects that may be relevant to aggressive behavior. We concluded that DLPFC tSMS modulated the network oscillations in regions distant from the location of stimulation and that tSMS has region specific effects on neural oscillations. Alec Sheffield, Sangtae Ahn, Sankaraleengam Alagapan, Flavio Fröhlich https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14232?af=R European Journal of Neuroscience Modulating neural oscillations by transcranial static magnetic field stimulation of the dorsolateral prefrontal cortex: A crossover, double‐blind, sham‐controlled pilot study

We applied transcranial static magnetic field stimulation to the dorsolateral prefrontal cortex and measured changes to neural oscillations. Contrary to prior findings of studies in the visual cortex, alpha power was unchanged at the site of stimulation, but we observed other alterations in the alpha, beta, and theta band. Our results indicate that the effect of transcranial static magnetic field stimulation on neural oscillations may be specific to the region stimulated.

 

Abstract

Transcranial static magnetic field stimulation (tSMS) is a novel non‐invasive brain stimulation technique that has been shown to locally increase alpha power in the parietal and occipital cortex. We investigated if tSMS locally increased alpha power in the left or right prefrontal cortex, as the balance of left/right prefrontal alpha power (frontal alpha asymmetry) has been linked to emotional processing and mood disorders. Therefore, altering frontal alpha asymmetry with tSMS may serve as a novel treatment to psychiatric diseases. We performed a crossover, double‐blind, sham‐controlled pilot study to assess the effects of prefrontal tSMS on neural oscillations. Twenty‐four right‐handed healthy participants were recruited and received left dorsolateral prefrontal cortex (DLPFC) tSMS, right DLPFC tSMS, and sham tSMS in a randomized order. Electroencephalography data were collected before (2 min eyes‐closed, 2 min eyes‐open), during (10 min eyes‐open), and after (2 min eyes‐open) stimulation. In contrast with our hypothesis, neither left nor right tSMS locally increased frontal alpha power. However, alpha power increased in occipital cortex during left DLPFC tSMS. Right DLPFC tSMS increased post‐stimulation fronto‐parietal theta power, indicating possible relevance to memory and cognition. Left and right DLPFC tSMS increased post‐stimulation left hemisphere beta power, indicating possible changes to motor behavior. Left DLPFC tSMS also increased post‐stimulation right frontal beta power, demonstrating complex network effects that may be relevant to aggressive behavior. We concluded that DLPFC tSMS modulated the network oscillations in regions distant from the location of stimulation and that tSMS has region specific effects on neural oscillations.

European Journal of Neuroscience, EarlyView. Modulating neural oscillations by transcranial static magnetic field stimulation of the dorsolateral prefrontal cortex: A crossover, double‐blind, sham‐controlled pilot study doi:10.1111/ejn.14232 European Journal of Neuroscience 2018-12-03T09:39:41-08:00 European Journal of Neuroscience 10.1111/ejn.14232 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14232?af=R RESEARCH REPORT Copper in the suprachiasmatic circadian clock: A possible link between multiple circadian oscillators Copper (Cu) levels homeostatically modulate SCN circadian clock phase through complex cellular mechanisms that overlap, yet are distinct from, those underlying photic phase regulation. Given Cu's ability to modulate cell metabolism, redox state, membrane excitability and transcription, it could help to link multiple circadian oscillators within the SCN and thereby strengthen its rhythmic output. Abstract The mammalian circadian clock in the suprachiasmatic nucleus (SCN) is very robust, able to coordinate our daily physiological and behavioral rhythms with exquisite accuracy. Simultaneously, the SCN clock is highly sensitive to environmental timing cues such as the solar cycle. This duality of resiliency and sensitivity may be sustained in part by a complex intertwining of three cellular oscillators: transcription/translation, metabolic/redox, and membrane excitability. We suggest here that one of the links connecting these oscillators may be forged from copper (Cu). Cellular Cu levels are highly regulated in the brain and peripherally, and Cu affects cellular metabolism, redox state, cell signaling, and transcription. We have shown that both Cu chelation and application induce nighttime phase shifts of the SCN clock in vitro and that these treatments affect glutamate, N‐methyl‐D‐aspartate receptor, and associated signaling processes differently. More recently we found that Cu induces mitogen‐activated protein kinase‐dependent phase shifts, while the mechanisms by which Cu removal induces phase shifts remain unclear. Lastly, we have found that two Cu transporters are expressed in the SCN, and that one of these transporters (ATP7A) exhibits a day/night rhythm. Our results suggest that Cu homeostasis is tightly regulated in the SCN, and that changes in Cu levels may serve as a time cue for the circadian clock. We discuss these findings in light of the existing literature and current models of multiple coupled circadian oscillators in the SCN. Yukihiro Yamada, Rebecca A. Prosser https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14181?af=R European Journal of Neuroscience Copper in the suprachiasmatic circadian clock: A possible link between multiple circadian oscillators

Copper (Cu) levels homeostatically modulate SCN circadian clock phase through complex cellular mechanisms that overlap, yet are distinct from, those underlying photic phase regulation. Given Cu's ability to modulate cell metabolism, redox state, membrane excitability and transcription, it could help to link multiple circadian oscillators within the SCN and thereby strengthen its rhythmic output.

 

Abstract

The mammalian circadian clock in the suprachiasmatic nucleus (SCN) is very robust, able to coordinate our daily physiological and behavioral rhythms with exquisite accuracy. Simultaneously, the SCN clock is highly sensitive to environmental timing cues such as the solar cycle. This duality of resiliency and sensitivity may be sustained in part by a complex intertwining of three cellular oscillators: transcription/translation, metabolic/redox, and membrane excitability. We suggest here that one of the links connecting these oscillators may be forged from copper (Cu). Cellular Cu levels are highly regulated in the brain and peripherally, and Cu affects cellular metabolism, redox state, cell signaling, and transcription. We have shown that both Cu chelation and application induce nighttime phase shifts of the SCN clock in vitro and that these treatments affect glutamate, N‐methyl‐D‐aspartate receptor, and associated signaling processes differently. More recently we found that Cu induces mitogen‐activated protein kinase‐dependent phase shifts, while the mechanisms by which Cu removal induces phase shifts remain unclear. Lastly, we have found that two Cu transporters are expressed in the SCN, and that one of these transporters (ATP7A) exhibits a day/night rhythm. Our results suggest that Cu homeostasis is tightly regulated in the SCN, and that changes in Cu levels may serve as a time cue for the circadian clock. We discuss these findings in light of the existing literature and current models of multiple coupled circadian oscillators in the SCN.

European Journal of Neuroscience, EarlyView. Copper in the suprachiasmatic circadian clock: A possible link between multiple circadian oscillators doi:10.1111/ejn.14181 European Journal of Neuroscience 2018-12-03T09:33:36-08:00 European Journal of Neuroscience 10.1111/ejn.14181 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14181?af=R SPECIAL ISSUE ARTICLE Metabolic and cardiovascular consequences of shift work: The role of circadian disruption and sleep disturbances Shift work inevitably leads to the displacement of rest‐activity, sleep–wake and fasting–feeding cycles. In turn, this may cause misalignment of the endogenous circadian timing system with the external environment as well as sleep disturbance. While accumulating evidence suggests that this has negative effects on cardiovascular and metabolic health, more research is required for the development and implementation of strategies that prevent or mitigate the adverse health effects of shift work. Abstract Shift work, defined as work occurring outside typical daytime working hours, is associated with an increased risk of various non‐communicable diseases, including diabetes and cardiovascular disease. Disruption of the internal circadian timing system and concomitant sleep disturbances is thought to play a critical role in the development of these health problems. Indeed, controlled laboratory studies have shown that short‐term circadian misalignment and sleep restriction independently impair physiological processes, including insulin sensitivity, energy expenditure, immune function, blood pressure and cardiac modulation by the autonomous nervous system. If allowed to persist, these acute effects may lead to the development of cardiometabolic diseases in the long term. Here, we discuss the evidence for the contributions of circadian disruption and associated sleep disturbances to the risk of metabolic and cardiovascular health problems in shift workers. Improving the understanding of the physiological mechanisms affected by circadian misalignment and sleep disturbance will contribute to the development and implementation of strategies that prevent or mitigate the cardiometabolic impact of shift work. Laura Kervezee, Anastasi Kosmadopoulos, Diane B. Boivin https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14216?af=R European Journal of Neuroscience Metabolic and cardiovascular consequences of shift work: The role of circadian disruption and sleep disturbances

Shift work inevitably leads to the displacement of rest‐activity, sleep–wake and fasting–feeding cycles. In turn, this may cause misalignment of the endogenous circadian timing system with the external environment as well as sleep disturbance. While accumulating evidence suggests that this has negative effects on cardiovascular and metabolic health, more research is required for the development and implementation of strategies that prevent or mitigate the adverse health effects of shift work.

 

Abstract

Shift work, defined as work occurring outside typical daytime working hours, is associated with an increased risk of various non‐communicable diseases, including diabetes and cardiovascular disease. Disruption of the internal circadian timing system and concomitant sleep disturbances is thought to play a critical role in the development of these health problems. Indeed, controlled laboratory studies have shown that short‐term circadian misalignment and sleep restriction independently impair physiological processes, including insulin sensitivity, energy expenditure, immune function, blood pressure and cardiac modulation by the autonomous nervous system. If allowed to persist, these acute effects may lead to the development of cardiometabolic diseases in the long term. Here, we discuss the evidence for the contributions of circadian disruption and associated sleep disturbances to the risk of metabolic and cardiovascular health problems in shift workers. Improving the understanding of the physiological mechanisms affected by circadian misalignment and sleep disturbance will contribute to the development and implementation of strategies that prevent or mitigate the cardiometabolic impact of shift work.

European Journal of Neuroscience, EarlyView. Metabolic and cardiovascular consequences of shift work: The role of circadian disruption and sleep disturbances doi:10.1111/ejn.14216 European Journal of Neuroscience 2018-12-03T09:29:15-08:00 European Journal of Neuroscience 10.1111/ejn.14216 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14216?af=R SPECIAL ISSUE REVIEW Metabotropic glutamate receptor 1‐mediated calcium mobilization in the neonatal hippocampal marginal zone Hippocampal marginal zone contains Cajal–Retzius cells and participates in regulation of cortical development. In these cells, intracellular Ca2+ elevation was detected after application of group I metabotropic glutamate receptor‐specific agonist (DHPG). This response was prevented by an antagonist of mGluR1 (CPCCOEt), indicating functional expression of this subtype of metabotropic receptor. Abstract The hippocampal marginal zone contains Cajal–Retzius (C‐R) cells and participates in the regulation of cortical development. Two subtypes of group I metabotropic glutamate receptors (mGluRs), mGluR1 and mGluR5, are found in the central nervous system and are considered to regulate neuronal excitability. The release of Ca2+ from intracellular stores is thought to be a main consequence of activation of these receptor subtypes. In hippocampal C‐R cells, the expression of mGluR1 has been showed using immunohistochemical techniques, but its function has not been elucidated. In this study, Ca2+ mobilization through mGluR1 activation was demonstrated in the neonatal rat hippocampus. In marginal zone C‐R cells, intracellular Ca2+ elevation was detected by fluorescence imaging after the application of a group I mGluR‐specific agonist. This response was prevented by application of an mGluR1 antagonist but was not changed by application of an mGluR5 antagonist. The intracellular Ca2+ elevation induced by mGluR1 activation was still observed in Ca2+‐free perfusate, indicating the release of Ca2+ from intracellular stores. γ‐Aminobutyric acid and ionotropic glutamate receptor‐mediated intracellular Ca2+ elevation was also detected in mGluR1‐possessing neurons, although the former was much smaller than that mediated by mGluR1. These results indicate that mGluR1 is functionally expressed in C‐R cells in the neonatal marginal zone and regulates cell function through the elevation of intracellular Ca2+. Megumi Taketo https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14200?af=R European Journal of Neuroscience Metabotropic glutamate receptor 1‐mediated calcium mobilization in the neonatal hippocampal marginal zone

Hippocampal marginal zone contains Cajal–Retzius cells and participates in regulation of cortical development. In these cells, intracellular Ca2+ elevation was detected after application of group I metabotropic glutamate receptor‐specific agonist (DHPG). This response was prevented by an antagonist of mGluR1 (CPCCOEt), indicating functional expression of this subtype of metabotropic receptor.

 

Abstract

The hippocampal marginal zone contains Cajal–Retzius (C‐R) cells and participates in the regulation of cortical development. Two subtypes of group I metabotropic glutamate receptors (mGluRs), mGluR1 and mGluR5, are found in the central nervous system and are considered to regulate neuronal excitability. The release of Ca2+ from intracellular stores is thought to be a main consequence of activation of these receptor subtypes. In hippocampal C‐R cells, the expression of mGluR1 has been showed using immunohistochemical techniques, but its function has not been elucidated. In this study, Ca2+ mobilization through mGluR1 activation was demonstrated in the neonatal rat hippocampus. In marginal zone C‐R cells, intracellular Ca2+ elevation was detected by fluorescence imaging after the application of a group I mGluR‐specific agonist. This response was prevented by application of an mGluR1 antagonist but was not changed by application of an mGluR5 antagonist. The intracellular Ca2+ elevation induced by mGluR1 activation was still observed in Ca2+‐free perfusate, indicating the release of Ca2+ from intracellular stores. γ‐Aminobutyric acid and ionotropic glutamate receptor‐mediated intracellular Ca2+ elevation was also detected in mGluR1‐possessing neurons, although the former was much smaller than that mediated by mGluR1. These results indicate that mGluR1 is functionally expressed in C‐R cells in the neonatal marginal zone and regulates cell function through the elevation of intracellular Ca2+.

European Journal of Neuroscience, Volume 48, Issue 11, Page 3344-3353, December 2018. Metabotropic glutamate receptor 1‐mediated calcium mobilization in the neonatal hippocampal marginal zone doi:10.1111/ejn.14200 European Journal of Neuroscience 2018-11-26T09:27:35-08:00 European Journal of Neuroscience 48 11 2018-12-01T08:00:00Z 2018-12-01T08:00:00Z 10.1111/ejn.14200 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14200?af=R RESEARCH REPORT Mutations in the guanylate cyclase gcy‐28 neuronally dissociate naïve attraction and memory retrieval Worms that lack the guanylate cyclase GCY‐28 have deficits in both naïve attraction to odors and associative learning. We have uncovered a novel role of GCY‐28 in the benzaldehyde/starvation memory retrieval pathway whereby it functions in the AIA interneurons to resolve the different signals from the AWCON and AWCOFF sensory neurons following their activation. Our results offer new insights about how information is processed in the neural network of C. elegans during associative learning. Abstract The molecules and mechanisms that are involved in the acquisition, storage, and retrieval of memories in many organisms are unclear. To investigate these processes, we use the nematode worm Caenorhabditis elegans, which is attracted naïvely to the odorant benzaldehyde but learns to avoid it after paired exposure with starvation. Mutations in the receptor‐like guanylate cyclase GCY‐28 have previously been thought to result in a behavioral switch in the primary chemosensory neuron AWCON, from an attractive state to an aversive (already‐learned) state. Here, we offer a different interpretation and show that GCY‐28 functions in distinct neurons to modulate two independent processes: naïve attraction to AWCON‐sensed odors in the AWCON neuron, and associative learning of benzaldehyde and starvation in the AIA interneurons. Consequently, mutants that lack gcy‐28 do not approach AWCON‐sensed odors and cannot associate benzaldehyde with starvation. We further show that this learning deficit lies in memory retrieval, not in its acquisition or storage, and that GCY‐28 is required in AIA for sensory integration only when both AWC neurons (ON and OFF) are activated by chemical stimuli. Our results reveal a novel role of GCY‐28 in the retrieval of associative memories and may have wide implications for the neural machineries of learning and memory in general. Naijin Li, Derek Kooy https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14221?af=R European Journal of Neuroscience Mutations in the guanylate cyclase gcy‐28 neuronally dissociate naïve attraction and memory retrieval

Worms that lack the guanylate cyclase GCY‐28 have deficits in both naïve attraction to odors and associative learning. We have uncovered a novel role of GCY‐28 in the benzaldehyde/starvation memory retrieval pathway whereby it functions in the AIA interneurons to resolve the different signals from the AWCON and AWCOFF sensory neurons following their activation. Our results offer new insights about how information is processed in the neural network of C. elegans during associative learning.

 

Abstract

The molecules and mechanisms that are involved in the acquisition, storage, and retrieval of memories in many organisms are unclear. To investigate these processes, we use the nematode worm Caenorhabditis elegans, which is attracted naïvely to the odorant benzaldehyde but learns to avoid it after paired exposure with starvation. Mutations in the receptor‐like guanylate cyclase GCY‐28 have previously been thought to result in a behavioral switch in the primary chemosensory neuron AWCON, from an attractive state to an aversive (already‐learned) state. Here, we offer a different interpretation and show that GCY‐28 functions in distinct neurons to modulate two independent processes: naïve attraction to AWCON‐sensed odors in the AWCON neuron, and associative learning of benzaldehyde and starvation in the AIA interneurons. Consequently, mutants that lack gcy‐28 do not approach AWCON‐sensed odors and cannot associate benzaldehyde with starvation. We further show that this learning deficit lies in memory retrieval, not in its acquisition or storage, and that GCY‐28 is required in AIA for sensory integration only when both AWC neurons (ON and OFF) are activated by chemical stimuli. Our results reveal a novel role of GCY‐28 in the retrieval of associative memories and may have wide implications for the neural machineries of learning and memory in general.

European Journal of Neuroscience, Volume 48, Issue 11, Page 3367-3378, December 2018. Mutations in the guanylate cyclase gcy‐28 neuronally dissociate naïve attraction and memory retrieval doi:10.1111/ejn.14221 European Journal of Neuroscience 2018-11-26T09:27:35-08:00 European Journal of Neuroscience 48 11 2018-12-01T08:00:00Z 2018-12-01T08:00:00Z 10.1111/ejn.14221 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14221?af=R RESEARCH REPORT Response anisocoria in the pupillary light and darkness reflex We demonstrated that the pupillary light and darkness reflexes had significantly larger ipsilateral responses compared to the contralateral responses relative to the stimulated visual field. The observed ipsilateral effects occurred significantly faster in the light than darkness reflex, suggesting that larger ipsilateral pupillary dilation after a luminance decrease cannot be only attributed to the inhibition of the parasympathetic system, but is also mediated by the excitation of the sympathetic system. Abstract The pupil constricts or dilates in response to a luminance increase or decrease, and these transient pupillary responses are controlled by the parasympathetic and sympathetic pathways. Although pupillary responses of the two eyes are highly correlated, they are not always identical (referred to as anisocoria). For example, there are unequal direct and consensual pupillary constriction responses after an increase in luminance to one eye. While contraction anisocoria (i.e. constriction) has been demonstrated in the pupillary light reflex, it is not yet known if there is also dilation anisocoria in the pupillary darkness reflex. Unlike previous studies that focused on the pupillary light reflex, we examined response anisocoria in both pupillary light and darkness reflexes. While requiring participants to maintain central fixation, we presented a light or dark stimulus to either the right or left visual field to induce transient pupillary constriction or dilation. Both the pupillary light and darkness reflexes had significantly larger ipsilateral responses compared to the contralateral responses relative to the stimulated visual field. The observed ipsilateral effects occurred significantly faster in the light than darkness reflex, suggesting that larger ipsilateral pupillary dilation after a luminance decrease cannot be only attributed to the inhibition of the parasympathetic system, but is also mediated by the excitation of the sympathetic system. Together, our results demonstrated a larger ipsilateral pupil response in both the pupillary light and darkness reflex, indicating an asymmetry in ipsilateral and contralateral neural circuitry of the pupillary darkness reflex. Chin‐An Wang, Leanne Tworzyanski, Jeff Huang, Douglas P. Munoz https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14195?af=R European Journal of Neuroscience Response anisocoria in the pupillary light and darkness reflex

We demonstrated that the pupillary light and darkness reflexes had significantly larger ipsilateral responses compared to the contralateral responses relative to the stimulated visual field. The observed ipsilateral effects occurred significantly faster in the light than darkness reflex, suggesting that larger ipsilateral pupillary dilation after a luminance decrease cannot be only attributed to the inhibition of the parasympathetic system, but is also mediated by the excitation of the sympathetic system.

 

Abstract

The pupil constricts or dilates in response to a luminance increase or decrease, and these transient pupillary responses are controlled by the parasympathetic and sympathetic pathways. Although pupillary responses of the two eyes are highly correlated, they are not always identical (referred to as anisocoria). For example, there are unequal direct and consensual pupillary constriction responses after an increase in luminance to one eye. While contraction anisocoria (i.e. constriction) has been demonstrated in the pupillary light reflex, it is not yet known if there is also dilation anisocoria in the pupillary darkness reflex. Unlike previous studies that focused on the pupillary light reflex, we examined response anisocoria in both pupillary light and darkness reflexes. While requiring participants to maintain central fixation, we presented a light or dark stimulus to either the right or left visual field to induce transient pupillary constriction or dilation. Both the pupillary light and darkness reflexes had significantly larger ipsilateral responses compared to the contralateral responses relative to the stimulated visual field. The observed ipsilateral effects occurred significantly faster in the light than darkness reflex, suggesting that larger ipsilateral pupillary dilation after a luminance decrease cannot be only attributed to the inhibition of the parasympathetic system, but is also mediated by the excitation of the sympathetic system. Together, our results demonstrated a larger ipsilateral pupil response in both the pupillary light and darkness reflex, indicating an asymmetry in ipsilateral and contralateral neural circuitry of the pupillary darkness reflex.

European Journal of Neuroscience, Volume 48, Issue 11, Page 3379-3388, December 2018. Response anisocoria in the pupillary light and darkness reflex doi:10.1111/ejn.14195 European Journal of Neuroscience 2018-11-26T09:27:35-08:00 European Journal of Neuroscience 48 11 2018-12-01T08:00:00Z 2018-12-01T08:00:00Z 10.1111/ejn.14195 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14195?af=R RESEARCH REPORT Purinergic modulation of neuronal activity in the rat prepositus hypoglossi nucleus Neurons in the prepositus hypoglossi nucleus (PHN) exhibited a fast inward (FI) current, a slow inward (SI) current, and/or a slow outward (SO) current in response to the ATP application. These current responses were also induced by 2‐meSATP, 2‐meSADP, and adenosine. These results, in addition to the results from other pharmacological analyses, indicate that the three current responses are mediated via P2X, P2Y, and P1 receptors. Abstract In the nervous system, adenosine 5′‐trisphosphate (ATP) functions as a neurotransmitter and binds to ionotropic P2X receptors and metabotropic P2Y receptors. Although ATP receptors are expressed in the prepositus hypoglossi nucleus (PHN), which is a brainstem structure involved in controlling horizontal gaze, it is unclear whether ATP indeed affects the activity of PHN neurons. In this study, we investigated the effects of ATP on spontaneous firing of PHN neurons using whole‐cell recordings in rat brainstem slices. Bath application of ATP increased or decreased the spontaneous firing rate of the neurons in a dose‐dependent manner, indicating that ATP indeed affects PHN neuronal activity. To clarify the mechanisms of the ATP effects, we investigated the current responses of PHN neurons to a local application of ATP. The ATP application induced a fast inward (FI) current, a slow inward (SI) current, and/or a slow outward (SO) current in the neurons. The agonists of P2X and P2Y receptors induced FI and SI currents, respectively. The SO currents were not induced by the ATP agonists but were induced by adenosine, which may be extracellularly converted from ATP by ectonucleotidases. An antagonist of adenosine P1 (A1) receptors abolished the adenosine‐induced SO currents and bath application of adenosine decreased the spontaneous firing rate of all PHN neurons tested. These results indicate that PHN neurons express functional purinoceptors and show that the FI, SI, and SO currents were mediated via P2X, P2Y, and A1 receptors, respectively. Miho Sugioka, Yasuhiko Saito https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14210?af=R European Journal of Neuroscience Purinergic modulation of neuronal activity in the rat prepositus hypoglossi nucleus

Neurons in the prepositus hypoglossi nucleus (PHN) exhibited a fast inward (FI) current, a slow inward (SI) current, and/or a slow outward (SO) current in response to the ATP application. These current responses were also induced by 2‐meSATP, 2‐meSADP, and adenosine. These results, in addition to the results from other pharmacological analyses, indicate that the three current responses are mediated via P2X, P2Y, and P1 receptors.

 

Abstract

In the nervous system, adenosine 5′‐trisphosphate (ATP) functions as a neurotransmitter and binds to ionotropic P2X receptors and metabotropic P2Y receptors. Although ATP receptors are expressed in the prepositus hypoglossi nucleus (PHN), which is a brainstem structure involved in controlling horizontal gaze, it is unclear whether ATP indeed affects the activity of PHN neurons. In this study, we investigated the effects of ATP on spontaneous firing of PHN neurons using whole‐cell recordings in rat brainstem slices. Bath application of ATP increased or decreased the spontaneous firing rate of the neurons in a dose‐dependent manner, indicating that ATP indeed affects PHN neuronal activity. To clarify the mechanisms of the ATP effects, we investigated the current responses of PHN neurons to a local application of ATP. The ATP application induced a fast inward (FI) current, a slow inward (SI) current, and/or a slow outward (SO) current in the neurons. The agonists of P2X and P2Y receptors induced FI and SI currents, respectively. The SO currents were not induced by the ATP agonists but were induced by adenosine, which may be extracellularly converted from ATP by ectonucleotidases. An antagonist of adenosine P1 (A1) receptors abolished the adenosine‐induced SO currents and bath application of adenosine decreased the spontaneous firing rate of all PHN neurons tested. These results indicate that PHN neurons express functional purinoceptors and show that the FI, SI, and SO currents were mediated via P2X, P2Y, and A1 receptors, respectively.

European Journal of Neuroscience, Volume 48, Issue 11, Page 3354-3366, December 2018. Purinergic modulation of neuronal activity in the rat prepositus hypoglossi nucleus doi:10.1111/ejn.14210 European Journal of Neuroscience 2018-11-26T09:27:35-08:00 European Journal of Neuroscience 48 11 2018-12-01T08:00:00Z 2018-12-01T08:00:00Z 10.1111/ejn.14210 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14210?af=R RESEARCH REPORT Suprachiasmatic function in a circadian period mutant: Duper alters light‐induced activation of vasoactive intestinal peptide cells and PERIOD1 immunostaining Duper mutant hamsters have a fast circadian clock and enhanced phase delays in response to a light pulse delivered in the early subjective night (Circadian Time 15). Top, the light signal is relayed from the eye to the suprachiasmatic nucleus (SCN), which serves as a master pacemaker. Subordinate circadian oscillators in other brain areas, including the paraventricular nucleus (PVN), adjust their phase in response to SCN input. As a result, behavioral rhythms show a phase delay (horizontal red arrow) that is greater in duper (middle panel) than wild‐type (bottom panel) hamsters. Resetting of the pacemaker of mutant hamsters differs from that in wild type: dupers show increased activation (as reflected by greater c‐FOS immunoreactivity) and clock gene expression (as reflected by PER1 immunoreactivity) in the ventral core (green) and dorsal shell (blue) neurons of the SCN at various time points sampled after the light pulse (vertical arrows). Activation of VIP neurons of the core SCN is specifically affected by the duper mutation. Abstract Mammalian circadian rhythms are entrained by photic stimuli that are relayed by retinal projections to the core of the suprachiasmatic nucleus (SCN). Neuronal activation, as demonstrated by expression of the immediate early gene c‐fos, leads to transcription of the core clock gene per1. The duper mutation in hamsters shortens circadian period and amplifies light‐induced phase shifts. We performed two experiments to compare the number of c‐FOS immunoreactive (ir) and PER1‐ir cells, and the intensity of staining, in the SCN of wild‐type (WT) and duper hamsters at various intervals after presentation of a 15‐min light pulse in the early subjective night. Light‐induced c‐FOS‐ir within 1 hr in the dorsocaudal SCN of duper, but not WT hamsters. In cells that express vasoactive intestinal peptide (VIP), which plays a critical role in synchronization of SCN cellular oscillators, light‐induced c‐FOS‐ir was greater in duper than WT hamsters. After the light pulse, PER1‐ir cells were found in more medial portions of the SCN than FOS‐ir, and appeared with a longer latency and over a longer time course, in VIP cells of duper than wild‐type hamsters. Our results indicate that the duper allele alters SCN function in ways that may contribute to changes in free running period and phase resetting. Emily N. C. Manoogian, Ajay Kumar, Doha Obed, Joseph Bergan, Eric L. Bittman https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14214?af=R European Journal of Neuroscience Suprachiasmatic function in a circadian period mutant: Duper alters light‐induced activation of vasoactive intestinal peptide cells and PERIOD1 immunostaining

Duper mutant hamsters have a fast circadian clock and enhanced phase delays in response to a light pulse delivered in the early subjective night (Circadian Time 15). Top, the light signal is relayed from the eye to the suprachiasmatic nucleus (SCN), which serves as a master pacemaker. Subordinate circadian oscillators in other brain areas, including the paraventricular nucleus (PVN), adjust their phase in response to SCN input. As a result, behavioral rhythms show a phase delay (horizontal red arrow) that is greater in duper (middle panel) than wild‐type (bottom panel) hamsters. Resetting of the pacemaker of mutant hamsters differs from that in wild type: dupers show increased activation (as reflected by greater c‐FOS immunoreactivity) and clock gene expression (as reflected by PER1 immunoreactivity) in the ventral core (green) and dorsal shell (blue) neurons of the SCN at various time points sampled after the light pulse (vertical arrows). Activation of VIP neurons of the core SCN is specifically affected by the duper mutation.

 

Abstract

Mammalian circadian rhythms are entrained by photic stimuli that are relayed by retinal projections to the core of the suprachiasmatic nucleus (SCN). Neuronal activation, as demonstrated by expression of the immediate early gene c‐fos, leads to transcription of the core clock gene per1. The duper mutation in hamsters shortens circadian period and amplifies light‐induced phase shifts. We performed two experiments to compare the number of c‐FOS immunoreactive (ir) and PER1‐ir cells, and the intensity of staining, in the SCN of wild‐type (WT) and duper hamsters at various intervals after presentation of a 15‐min light pulse in the early subjective night. Light‐induced c‐FOS‐ir within 1 hr in the dorsocaudal SCN of duper, but not WT hamsters. In cells that express vasoactive intestinal peptide (VIP), which plays a critical role in synchronization of SCN cellular oscillators, light‐induced c‐FOS‐ir was greater in duper than WT hamsters. After the light pulse, PER1‐ir cells were found in more medial portions of the SCN than FOS‐ir, and appeared with a longer latency and over a longer time course, in VIP cells of duper than wild‐type hamsters. Our results indicate that the duper allele alters SCN function in ways that may contribute to changes in free running period and phase resetting.

European Journal of Neuroscience, Volume 48, Issue 11, Page 3319-3334, December 2018. Suprachiasmatic function in a circadian period mutant: Duper alters light‐induced activation of vasoactive intestinal peptide cells and PERIOD1 immunostaining doi:10.1111/ejn.14214 European Journal of Neuroscience 2018-11-26T09:27:35-08:00 European Journal of Neuroscience 48 11 2018-12-01T08:00:00Z 2018-12-01T08:00:00Z 10.1111/ejn.14214 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14214?af=R RESEARCH REPORT The role of the dorsolateral prefrontal cortex in the motor placebo effect The placebo effect is a beneficial outcome that follows the application of an inert treatment together with verbal suggestion of improvement (a). Here, we tested the hypothesis that the dlPFC (stimulated with tDCS) plays a role in the motor placebo effect in a force task (b). In placebo‐responders, force increased after the placebo procedure with sham tDCS (c), whereas it remained stable with active tDCS (d). The dlPFC plays a role in the motor placebo effect evoked by verbal suggestion alone. Abstract The neural correlates of the placebo effect in the motor domain are still unknown. The aim of this study was to tackle the role of a frontal cortical region, the dorsolateral prefrontal cortex (dlPFC). To this end, we stimulated the cortical site corresponding to the left dlPFC with transcranial direct current stimulation (tDCS) during a placebo procedure and measured any change in the motor placebo effect in all the participants and more specifically in placebo‐responders. Three different experiments were conducted in which healthy volunteers performed a force motor task with the index finger. The placebo treatment consisted of transcutaneous electrical nerve stimulation (TENS). In Experiment 1 (expectation alone), participants were only verbally suggested about the positive effects of TENS. In Experiment 2 (expectation and conditioning), participants were verbally suggested about TENS and conditioned with a surreptitious increase in a visual feedback of force. In Experiment 3 (control procedure), participants were told that TENS was inefficient. Each participant was tested in three different days with anodal, cathodal and sham tDCS over the dlPFC. Results showed that in Experiment 1 and 2 force increased after the procedure, independently of tDCS. By focusing on placebo‐responders, we found that in Experiment 1 force remained stable after active tDCS, whereas it increased after inactive tDCS. These findings bring new evidence on the neural underpinnings of the motor placebo effect, by showing that independently of the polarity, active tDCS over the left dlPFC may undermine the expectation‐induced enhancement of force in placebo‐responders. Bernardo Villa‐Sánchez, Mehran Emadi Andani, Mirta Fiorio https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14217?af=R European Journal of Neuroscience The role of the dorsolateral prefrontal cortex in the motor placebo effect

The placebo effect is a beneficial outcome that follows the application of an inert treatment together with verbal suggestion of improvement (a). Here, we tested the hypothesis that the dlPFC (stimulated with tDCS) plays a role in the motor placebo effect in a force task (b). In placebo‐responders, force increased after the placebo procedure with sham tDCS (c), whereas it remained stable with active tDCS (d). The dlPFC plays a role in the motor placebo effect evoked by verbal suggestion alone.

 

Abstract

The neural correlates of the placebo effect in the motor domain are still unknown. The aim of this study was to tackle the role of a frontal cortical region, the dorsolateral prefrontal cortex (dlPFC). To this end, we stimulated the cortical site corresponding to the left dlPFC with transcranial direct current stimulation (tDCS) during a placebo procedure and measured any change in the motor placebo effect in all the participants and more specifically in placebo‐responders. Three different experiments were conducted in which healthy volunteers performed a force motor task with the index finger. The placebo treatment consisted of transcutaneous electrical nerve stimulation (TENS). In Experiment 1 (expectation alone), participants were only verbally suggested about the positive effects of TENS. In Experiment 2 (expectation and conditioning), participants were verbally suggested about TENS and conditioned with a surreptitious increase in a visual feedback of force. In Experiment 3 (control procedure), participants were told that TENS was inefficient. Each participant was tested in three different days with anodal, cathodal and sham tDCS over the dlPFC. Results showed that in Experiment 1 and 2 force increased after the procedure, independently of tDCS. By focusing on placebo‐responders, we found that in Experiment 1 force remained stable after active tDCS, whereas it increased after inactive tDCS. These findings bring new evidence on the neural underpinnings of the motor placebo effect, by showing that independently of the polarity, active tDCS over the left dlPFC may undermine the expectation‐induced enhancement of force in placebo‐responders.

European Journal of Neuroscience, Volume 48, Issue 11, Page 3410-3425, December 2018. The role of the dorsolateral prefrontal cortex in the motor placebo effect doi:10.1111/ejn.14217 European Journal of Neuroscience 2018-11-26T09:27:35-08:00 European Journal of Neuroscience 48 11 2018-12-01T08:00:00Z 2018-12-01T08:00:00Z 10.1111/ejn.14217 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14217?af=R Research Report Anorexia nervosa or starvation? Andrea Phillipou, Susan Lee Rossell, David Jonathan Castle https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14158?af=R European Journal of Neuroscience, Volume 48, Issue 11, Page 3317-3318, December 2018. Anorexia nervosa or starvation? doi:10.1111/ejn.14158 European Journal of Neuroscience 2018-11-26T09:27:35-08:00 European Journal of Neuroscience 48 11 2018-12-01T08:00:00Z 2018-12-01T08:00:00Z 10.1111/ejn.14158 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14158?af=R EDITORIAL Issue Information https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14277?af=R European Journal of Neuroscience, Volume 48, Issue 11, Page i-iii, December 2018. Issue Information doi:10.1111/ejn.14277 European Journal of Neuroscience 2018-11-26T09:27:35-08:00 European Journal of Neuroscience 48 11 2018-12-01T08:00:00Z 2018-12-01T08:00:00Z 10.1111/ejn.14277 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14277?af=R ISSUE INFORMATION Asymmetries of the visual system and their influence on visual performance and oculomotor dynamics We review evidence for asymmetries in vision, attention, and oculomotor behaviour. We mainly focus on processing differences that can be traced to asymmetries of the visual system, in particular nasal‐temporal asymmetries. Biological asymmetries are found in the retina, the optic nerves and some brain areas involved in visual processing, and these asymmetries manifest in various measures, basic psychophysical tests of attentional processing, choice behaviour, and saccadic parameters. Abstract Our representation of the visual field is not homogenous. There are differences in resolution not only between the fovea and regions eccentric to it, but also between the nasal and temporal hemiretinae, that can be traced to asymmetric distributions of photoreceptors and ganglion cells. We review evidence for differences in visual and attentional processing and oculomotor behaviour that can be traced to asymmetries of the visual system, mainly emphasising nasal‐temporal asymmetries. Asymmetries in the visual system manifest in various measures, in basic psychophysical tests of visual performance, attentional processing, choice behaviour, saccadic peak velocity, and latencies. Nasal‐temporal asymmetries on saccadic latency seem primarily to occur for express saccades. Neural asymmetries between the upper and lower hemifields are strong and cause corresponding differences in performance between the hemifields. There are interesting individual differences in asymmetric processing which seem to be related to the strength of eye dominance. These neurophysiological asymmetries and the corresponding asymmetries in visual performance and oculomotor behaviour can strongly influence experimental results in vision and must be considered during experimental design and the interpretation of results. Ómar I. Jóhannesson, Jérôme Tagu, Árni Kristjánsson https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14225?af=R European Journal of Neuroscience Asymmetries of the visual system and their influence on visual performance and oculomotor dynamics

We review evidence for asymmetries in vision, attention, and oculomotor behaviour. We mainly focus on processing differences that can be traced to asymmetries of the visual system, in particular nasal‐temporal asymmetries. Biological asymmetries are found in the retina, the optic nerves and some brain areas involved in visual processing, and these asymmetries manifest in various measures, basic psychophysical tests of attentional processing, choice behaviour, and saccadic parameters.

 

Abstract

Our representation of the visual field is not homogenous. There are differences in resolution not only between the fovea and regions eccentric to it, but also between the nasal and temporal hemiretinae, that can be traced to asymmetric distributions of photoreceptors and ganglion cells. We review evidence for differences in visual and attentional processing and oculomotor behaviour that can be traced to asymmetries of the visual system, mainly emphasising nasal‐temporal asymmetries. Asymmetries in the visual system manifest in various measures, in basic psychophysical tests of visual performance, attentional processing, choice behaviour, saccadic peak velocity, and latencies. Nasal‐temporal asymmetries on saccadic latency seem primarily to occur for express saccades. Neural asymmetries between the upper and lower hemifields are strong and cause corresponding differences in performance between the hemifields. There are interesting individual differences in asymmetric processing which seem to be related to the strength of eye dominance. These neurophysiological asymmetries and the corresponding asymmetries in visual performance and oculomotor behaviour can strongly influence experimental results in vision and must be considered during experimental design and the interpretation of results.

European Journal of Neuroscience, Volume 48, Issue 11, Page 3426-3445, December 2018. Asymmetries of the visual system and their influence on visual performance and oculomotor dynamics doi:10.1111/ejn.14225 European Journal of Neuroscience 2018-11-26T09:27:35-08:00 European Journal of Neuroscience 48 11 2018-12-01T08:00:00Z 2018-12-01T08:00:00Z 10.1111/ejn.14225 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14225?af=R REVIEW ARTICLE Assessment of ventral tegmental area‐projecting GABAergic neurons from the bed nucleus of the stria terminalis in modulating binge‐like ethanol intake This study shows that chemogenetic silencing of ventral tegmental area‐projecting GABAergic neurons of the dorsal lateral bed nucleus of the stria terminalis blunts binge‐like ethanol consumption and not sucrose consumption in mice. This GABAergic population co‐expresses corticotropin‐releasing factor, a population which we have previously shown to modulate binge‐like ethanol intake. Characterization of this neurocircuitry may provide valuable insight into the mechanisms underlying the development of alcohol use disorders. Abstract Corticotropin‐releasing factor (CRF) circuitry is a key component in plasticity underlying the transition to ethanol (EtOH) dependence. We have previously shown that chemogenetic silencing of CRF neurons stemming from the dorsolateral bed nucleus of the stria terminalis (dlBNST) and projecting to the ventral tegmental area (VTA) significantly blunts binge‐like EtOH consumption. While CRF neurons in the BNST are thought to entail primarily a GABA phenotype, glutamatergic neurons within the BNST also innervate the VTA and influence consummatory behaviors. Here, we combined the well‐validated Vgat‐ires‐Cre transgenic mice with chemogenetic tools to extend our previous findings and corroborate the contribution of the VTA‐projecting dlBNST GABAergic circuitry in modulating binge‐like EtOH consumption using “drinking‐in‐the‐dark” procedures. Mice were given bilateral injection of Gi‐coupled chemogenetic viral vector (or control virus) into the dlBNST and bilateral cannulae into the VTA. On test day, clozapine‐N‐oxide (CNO; or vehicle) was infused directly into the VTA to silence VTA‐projecting dlBNST neurons and subsequent binge‐like EtOH consumption was assessed. We then used immunohistochemistry (IHC) to determine the co‐expression of CRF and viral vector. Our results showed that relative to vehicle treatment or CNO treatment in mice expressing the control virus, silencing VTA‐projecting dlBNST GABAergic neurons by CNO treatment in mice expressing Gi‐coupled chemogenetic virus significantly reduced binge‐like EtOH intake. This effect was not seen with sucrose consumption. Our IHC results confirm a population of CRF‐expressing GABAergic neurons within the dlBNST. This study directly establishes that VTA‐projecting GABAergic neurons of the dlBNST modulate binge‐like EtOH consumption. Michel A. Companion, Todd E. Thiele https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14222?af=R European Journal of Neuroscience Assessment of ventral tegmental area‐projecting GABAergic neurons from the bed nucleus of the stria terminalis in modulating binge‐like ethanol intake

This study shows that chemogenetic silencing of ventral tegmental area‐projecting GABAergic neurons of the dorsal lateral bed nucleus of the stria terminalis blunts binge‐like ethanol consumption and not sucrose consumption in mice. This GABAergic population co‐expresses corticotropin‐releasing factor, a population which we have previously shown to modulate binge‐like ethanol intake. Characterization of this neurocircuitry may provide valuable insight into the mechanisms underlying the development of alcohol use disorders.

 

Abstract

Corticotropin‐releasing factor (CRF) circuitry is a key component in plasticity underlying the transition to ethanol (EtOH) dependence. We have previously shown that chemogenetic silencing of CRF neurons stemming from the dorsolateral bed nucleus of the stria terminalis (dlBNST) and projecting to the ventral tegmental area (VTA) significantly blunts binge‐like EtOH consumption. While CRF neurons in the BNST are thought to entail primarily a GABA phenotype, glutamatergic neurons within the BNST also innervate the VTA and influence consummatory behaviors. Here, we combined the well‐validated Vgat‐ires‐Cre transgenic mice with chemogenetic tools to extend our previous findings and corroborate the contribution of the VTA‐projecting dlBNST GABAergic circuitry in modulating binge‐like EtOH consumption using “drinking‐in‐the‐dark” procedures. Mice were given bilateral injection of Gi‐coupled chemogenetic viral vector (or control virus) into the dlBNST and bilateral cannulae into the VTA. On test day, clozapine‐N‐oxide (CNO; or vehicle) was infused directly into the VTA to silence VTA‐projecting dlBNST neurons and subsequent binge‐like EtOH consumption was assessed. We then used immunohistochemistry (IHC) to determine the co‐expression of CRF and viral vector. Our results showed that relative to vehicle treatment or CNO treatment in mice expressing the control virus, silencing VTA‐projecting dlBNST GABAergic neurons by CNO treatment in mice expressing Gi‐coupled chemogenetic virus significantly reduced binge‐like EtOH intake. This effect was not seen with sucrose consumption. Our IHC results confirm a population of CRF‐expressing GABAergic neurons within the dlBNST. This study directly establishes that VTA‐projecting GABAergic neurons of the dlBNST modulate binge‐like EtOH consumption.

European Journal of Neuroscience, Volume 48, Issue 11, Page 3335-3343, December 2018. Assessment of ventral tegmental area‐projecting GABAergic neurons from the bed nucleus of the stria terminalis in modulating binge‐like ethanol intake doi:10.1111/ejn.14222 European Journal of Neuroscience 2018-11-26T09:27:35-08:00 European Journal of Neuroscience 48 11 2018-12-01T08:00:00Z 2018-12-01T08:00:00Z 10.1111/ejn.14222 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14222?af=R SHORT COMMUNICATION Neural basis of goal‐driven changes in knowledge activation We used representational similarity analysis to demonstrate that the relationship between brain activity and semantic structure varies, depending on the degree to which knowledge is accessed. During semantic, but not episodic, judgments, activity in a left‐lateralized network associated with semantic memory correlated with semantic structure. The present results illustrate how knowledge storage and retrieval shapes our understanding and long‐term memory. Abstract Depending on a person's goals, different aspects of stored knowledge are accessed. Decades of behavioral work document the flexible use of knowledge, but little neuroimaging work speaks to these questions. We used representational similarity analysis to investigate whether the relationship between brain activity and semantic structure of statements varied in two tasks hypothesized to differ in the degree to which knowledge is accessed: judging truth (semantic task) and judging oldness (episodic task). During truth judgments, but not old/new recognition judgments, a left‐lateralized network previously associated with semantic memory exhibited correlations with semantic structure. At a neural level, people activate knowledge representations in different ways when focused on different goals. The present results demonstrate the potential of multivariate approaches in characterizing knowledge storage and retrieval, as well as the ways that it shapes our understanding and long‐term memory. Wei‐Chun Wang, Nadia M. Brashier, Erik A. Wing, Elizabeth J. Marsh, Roberto Cabeza https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14196?af=R European Journal of Neuroscience Neural basis of goal‐driven changes in knowledge activation

We used representational similarity analysis to demonstrate that the relationship between brain activity and semantic structure varies, depending on the degree to which knowledge is accessed. During semantic, but not episodic, judgments, activity in a left‐lateralized network associated with semantic memory correlated with semantic structure. The present results illustrate how knowledge storage and retrieval shapes our understanding and long‐term memory.

 

Abstract

Depending on a person's goals, different aspects of stored knowledge are accessed. Decades of behavioral work document the flexible use of knowledge, but little neuroimaging work speaks to these questions. We used representational similarity analysis to investigate whether the relationship between brain activity and semantic structure of statements varied in two tasks hypothesized to differ in the degree to which knowledge is accessed: judging truth (semantic task) and judging oldness (episodic task). During truth judgments, but not old/new recognition judgments, a left‐lateralized network previously associated with semantic memory exhibited correlations with semantic structure. At a neural level, people activate knowledge representations in different ways when focused on different goals. The present results demonstrate the potential of multivariate approaches in characterizing knowledge storage and retrieval, as well as the ways that it shapes our understanding and long‐term memory.

European Journal of Neuroscience, Volume 48, Issue 11, Page 3389-3396, December 2018. Neural basis of goal‐driven changes in knowledge activation doi:10.1111/ejn.14196 European Journal of Neuroscience 2018-11-26T09:27:35-08:00 European Journal of Neuroscience 48 11 2018-12-01T08:00:00Z 2018-12-01T08:00:00Z 10.1111/ejn.14196 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14196?af=R SHORT COMMUNICATION Task errors contribute to implicit aftereffects in sensorimotor adaptation We manipulated the intrinsic reward of hitting or missing targets during target‐reaching in sensorimotor adaptation. The intrinsic reward of hitting/missing targets affects implicit aftereffects resulting from exposure to sensory prediction errors. Hence, rewards might contribute to changes in implicit aftereffects, possibly by increasing sensitivity to sensory prediction errors. Abstract Perturbations of sensory feedback evoke sensory prediction errors (discrepancies between predicted and actual sensory outcomes of movements), and reward prediction errors (discrepancies between predicted rewards and actual rewards). When our task is to hit a target, we expect to succeed in hitting the target, and so we experience a reward prediction error if the perturbation causes us to miss it. These discrepancies between intended task outcomes and actual task outcomes, termed “task errors,” are thought to drive the use of strategic processes to restore success, although their role is incompletely understood. Here, as participants adapted to a 30° rotation of cursor feedback representing hand position, we investigated the role of task errors in sensorimotor adaptation: during target‐reaching, we either removed task errors by moving the target mid‐movement to align with cursor feedback of hand position, or enforced task error by moving the target away from the cursor feedback of hand position, by 20–30° randomly (clockwise in half the trials, counterclockwise in half the trials). Removing task errors not only reduced the extent of adaptation during exposure to the perturbation, but also reduced the amount of post‐adaptation aftereffects that persisted despite explicit knowledge of the perturbation removal. Hence, task errors contribute to implicit adaptation resulting from sensory prediction errors. This suggests that the system which predicts the sensory consequences of actions via exposure to sensory prediction errors is also sensitive to reward prediction errors. Li‐Ann Leow, Welber Marinovic, Aymar Rugy, Timothy J. Carroll https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14213?af=R European Journal of Neuroscience Task errors contribute to implicit aftereffects in sensorimotor adaptation

We manipulated the intrinsic reward of hitting or missing targets during target‐reaching in sensorimotor adaptation. The intrinsic reward of hitting/missing targets affects implicit aftereffects resulting from exposure to sensory prediction errors. Hence, rewards might contribute to changes in implicit aftereffects, possibly by increasing sensitivity to sensory prediction errors.

 

Abstract

Perturbations of sensory feedback evoke sensory prediction errors (discrepancies between predicted and actual sensory outcomes of movements), and reward prediction errors (discrepancies between predicted rewards and actual rewards). When our task is to hit a target, we expect to succeed in hitting the target, and so we experience a reward prediction error if the perturbation causes us to miss it. These discrepancies between intended task outcomes and actual task outcomes, termed “task errors,” are thought to drive the use of strategic processes to restore success, although their role is incompletely understood. Here, as participants adapted to a 30° rotation of cursor feedback representing hand position, we investigated the role of task errors in sensorimotor adaptation: during target‐reaching, we either removed task errors by moving the target mid‐movement to align with cursor feedback of hand position, or enforced task error by moving the target away from the cursor feedback of hand position, by 20–30° randomly (clockwise in half the trials, counterclockwise in half the trials). Removing task errors not only reduced the extent of adaptation during exposure to the perturbation, but also reduced the amount of post‐adaptation aftereffects that persisted despite explicit knowledge of the perturbation removal. Hence, task errors contribute to implicit adaptation resulting from sensory prediction errors. This suggests that the system which predicts the sensory consequences of actions via exposure to sensory prediction errors is also sensitive to reward prediction errors.

European Journal of Neuroscience, Volume 48, Issue 11, Page 3397-3409, December 2018. Task errors contribute to implicit aftereffects in sensorimotor adaptationdoi:10.1111/ejn.14213European Journal of Neuroscience2018-11-26T12:00:00-08:00European Journal of Neuroscience48112018-12-01T08:00:00Z2018-12-01T08:00:00Z10.1111/ejn.14213 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14213?af=RRESEARCH REPORT The circadian gene Nr1d1 in the mouse nucleus accumbens modulates sociability and anxiety‐related behavior Abstract Nuclear receptor subfamily 1, group D, member 1 (Nr1d1) (also known as Rev‐erb alpha) has been linked to circadian rhythm regulation, mood‐related behavior, and disorders associated with social deficits. Recent work from our laboratory found striking decreases in Nr1d1 in the nucleus accumbens (NAc) in the maternal condition and indirect evidence that Nr1d1 was interacting with numerous addiction and reward‐related genes to modulate social reward. In this study, we applied our insights from the maternal state to non‐parental adult mice to determine whether decreases in Nr1d1 expression in the NAc via adeno‐associated viral (AAV) vectors and short hairpin RNA (shRNA)‐mediated gene knockdown were sufficient to modulate social behaviors and mood‐related behaviors. Knockdown of Nr1d1 in the NAc enhanced sociability, reduced anxiety, but did not affect depressive‐like traits in female mice. In male mice, Nr1d1 knockdown had no significant behavioral effects. Microarray analysis of Nr1d1 knockdown in females identified changes in circadian rhythm and histone deacetylase genes and suggested possible drugs, including histone deacetylase inhibitors, that could mimic actions of Nr1d1 knockdown. Quantitative real‐time PCR (qPCR) analysis confirmed expression upregulation of genes period circadian clock 1 (Per1) and period circadian clock 2 (Per2) with Nr1d1 knockdown. Evidence for roles for opioid‐related genes opioid receptor, delta 1 (Oprd1) and preproenkephalin (Penk) was also found. Together, these results suggest that Nr1d1 in the NAc modulates sociability and anxiety‐related behavior in a sex‐specific manner and circadian, histone deacetylase, and opioid‐related genes may be involved in the expression of these behavioral phenotypes. This article is protected by copyright. All rights reserved. Changjiu Zhao, Stephen C Gammie https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14207?af=R

Abstract

Nuclear receptor subfamily 1, group D, member 1 (Nr1d1) (also known as Rev‐erb alpha) has been linked to circadian rhythm regulation, mood‐related behavior, and disorders associated with social deficits. Recent work from our laboratory found striking decreases in Nr1d1 in the nucleus accumbens (NAc) in the maternal condition and indirect evidence that Nr1d1 was interacting with numerous addiction and reward‐related genes to modulate social reward. In this study, we applied our insights from the maternal state to non‐parental adult mice to determine whether decreases in Nr1d1 expression in the NAc via adeno‐associated viral (AAV) vectors and short hairpin RNA (shRNA)‐mediated gene knockdown were sufficient to modulate social behaviors and mood‐related behaviors. Knockdown of Nr1d1 in the NAc enhanced sociability, reduced anxiety, but did not affect depressive‐like traits in female mice. In male mice, Nr1d1 knockdown had no significant behavioral effects. Microarray analysis of Nr1d1 knockdown in females identified changes in circadian rhythm and histone deacetylase genes and suggested possible drugs, including histone deacetylase inhibitors, that could mimic actions of Nr1d1 knockdown. Quantitative real‐time PCR (qPCR) analysis confirmed expression upregulation of genes period circadian clock 1 (Per1) and period circadian clock 2 (Per2) with Nr1d1 knockdown. Evidence for roles for opioid‐related genes opioid receptor, delta 1 (Oprd1) and preproenkephalin (Penk) was also found. Together, these results suggest that Nr1d1 in the NAc modulates sociability and anxiety‐related behavior in a sex‐specific manner and circadian, histone deacetylase, and opioid‐related genes may be involved in the expression of these behavioral phenotypes.

This article is protected by copyright. All rights reserved.

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-. The circadian gene Nr1d1 in the mouse nucleus accumbens modulates sociability and anxiety‐related behavior doi:10.1111/ejn.14207 European Journal of Neuroscience 2018-10-16T10:39:16-07:00 European Journal of Neuroscience 10.1111/ejn.14207 https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14207?af=R Research Report

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