Job ID: 106512
PhD project –Hippocampal dynamics in health and ASD during the first two postnatal weeks
Position: Ph.D. Student
Deadline: 2 April 2023
Employment Start Date: 2 October 2023
Contract Length: 3 years
Institution: Aix Marseille Université
Department: INMED, INSERM
The NeuroSchool PhD Program of Aix-Marseille University (France) has launched its annual calls for PhD scholarships for students with a master’s degree in a non-French university.
The following project is one of the 14 proposed projects. Not all proposed projects will be funded, check our website for details.
RESEARCH PROJECT :
- State of the art
The human hippocampus is crucial for the storage of events into episodic memory. The fact that human episodic memory improves with development and is only partially functional in infancy suggests that hippocampal representations may be very different at early postnatal age. Indeed, it has been suggested that the hippocampus, in addition to being a cognitive region, should also be considered as a sensorimotor structure (Bland and Oddie, 2001; Del Rio-Bermudez and Blumberg, 2021). We and others, have recently shown that this is particularly true during development, when self-triggered sensorimotor inputs (in the form of spontaneous myoclonic movements, such as twitches) drive CA1 dynamics (Mohns and Blumberg, 2008; Dard et al., 2022) and may contribute to the development and maturation of the hippocampal circuitry. More specifically, my group has shown that the first postnatal week ends with a change in the hippocampal representation of sensorimotor inputs with most pyramidal cells switching from being activated to being inhibited by self-generated spontaneous movements whereas interneurons remain activated. We also demonstrated that this change is mediated by the rapid anatomical sprouting of peri-somatic GABAergic innervation of pyramidal cells by parvalbumin basket cells (PVBC, Figure 1, bottom panels represented in red), in agreement with theoretical predictions from a computational model. Furthermore, unpublished data from my group indicate that around P9: 1- the frequency of spontaneous myoclonic movements is reduced in an animal model of ASD; 2- PVBC perisomatic innervation is reduced in the same model of ASD. Of note, this stage (P9) marks a salient checkpoint when both parameters significantly impact CA1 dynamics. Based on these findings, our project is well positioned to address how hippocampal development is affected in mouse models of ASD (“outstanding question” in a recent review (Banker et al., 2021)).
Since the diagnosis of autism is largely based on behavioral assessment, we first plan to quantify several aspects of mouse behavior in ASD during development. Then, we will test the hypothesis that the transition observed between the first two postnatal weeks is affected in mouse models of ASD. Finally, we will probe the circuit mechanisms supporting this transition both in wild type and ASD mouse model.
To address these questions, we will use a combination of in-vivo two-photon microscopy, behavioral and electrophysiological recordings, and anatomical characterization during the first two postnatal weeks.
- Expected candidate profile
We are looking for a motivated student with either a neurobiology background with a keen interest in computational neuroscience or a physics student with interest in neurobiology and experimentation.