Job ID: 106470

PhD project – Plasticity of intrinsic neuronal excitability in visual thalamic neurons

Position: Ph.D. Student

Deadline: 2 April 2023

Employment Start Date: 2 October 2023

Contract Length: 3 years

City: Marseille

Country: France

Institution: Aix Marseille Université

Department: UNIS

Description:

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 dorsal lateral geniculate nucleus (dLGN), a primary recipient structure of retinal inputs, is traditionally considered to be just a relay of visual information. However, recent works indicate that dLGN expresses functional plasticity following monocular deprivation (MD; Jaepel et al., Nat Neurosci 2017; Sommeijer et al., Nat Neurosci 2017). The cellular and molecular substrate of this plasticity has not been idendified.

Objectives. Our proposal therefore consists in testing whether visual and spiking activity may modify neuronal excitability in dLGN neurons. We propose to i) determine the mechanisms of long-term potentiation of intrinsic excitability (LTP-IE) in dLGN relay cells and GABAergic interneurons, and ii) define the structural correlate and the molecular mechanisms of the homeostatic plasticity of intrinsic excitability observed following MD.

Methods. To characterize the induction and expression mechanisms of LTP-IE in dLGN neurons, a combination of electrophysiological recordings in acute or cultured slices and of pharmacological tools, CRISPR/Cas9, calcium imaging and calcium uncaging will be used.

Expected results. Homeostatic plasticity may regulate both voltage-gated channels at the AIS and/or passive membrane properties. We will therefore analyze the changes in spike threshold and passive membrane properties (input resistance and membrane capacitance) of the neurons after various delays of MD on the deprived and spared regions of the dLGN. A lower spike threshold is expected for homeostatic compensation whereas a higher spike threshold is expected for Hebbian plasticity. No change in passive properties is expected after homeostatic and Hebbian plasticity.

Feasibility. This research project is largely feasible as we already obtained preliminary results showing that homeostatic regulation of neuronal excitability is observed after 4 days of MD but that Hebbian regulation is found after 10 days of MD. To understand whether LTP-IE and MD-induced plasticity of IE share common expression mechanisms in dLGN neurons, we will test whether the magnitude of LTP-IE is changed after MD. In particular, we will check LTP-IE magnitude in neurons from the deprived and spared regions of the dLGN after 4 and 10 days of MD. An increase in LTP-IE is expected in neurons that underwent a reduction in IE (i.e. open side at 4 days of MD or deprived side at 10 days of MD) and the opposite effect in neurons that underwent an increase in IE.

Expected candidate profile. For this project, the candidate will have to be interested in cellular physiology and should have at least a theoretical background in electrophysiology. Skills in immunohistochemistry, molecular biology and cellular biology may be a plus.