Job ID: 122252

PhD position – Role of Nav1.2 sodium channels in the activity and morphology of dopaminergic neurons

Position: Ph.D. Student

Deadline: 14 April 2025

Employment Start Date: 1 October 2025

Contract Length: 3 years

City: Marseille

Country: France

Institution: Aix-Marseille University

Department: INT

Description:

The NeuroSchool PhD Program of Aix-Marseille University (France) has launched its annual calls for PhD contracts for students with a master’s degree in a non-French university and for   international co-supervised PhDs.

This project is one of the proposed projects. Not all proposed projects will be funded, check our website for details.

Midbrain dopaminergic (DA) neurons and in particular those located in the substantia nigra pars compacta (SNc) play an essential role in the control of striatal activity and motor execution. The degeneration of SNc DA neurons is one of the early features of Parkinson’s disease and explains most of the motor deficits observed in this pathology. A number of studies have suggested that SNc DA neurons might degenerate because of their peculiar pattern of activity and electrophysiological characteristics, such as their broad action potential and autonomous pacemaking firing. Our previous work (Moubarak, 2019, 2022, 2025) has demonstrated that somatodendritic sodium channels play an essential role in the genesis of these electrophysiological properties. Understanding the nature and role of these sodium channels might shed light on the vulnerability of this cell type in pathological conditions. We propose to extend and refine these studies by using a transgenic mouse carrying a deletion of Nav1.2 sodium channels specifically in DA neurons. Our recent work indeed suggests that the loss of Nav1.2 not only strongly modifies the activity of these neurons but also affects their morphology. The methodology proposed relies on electrophysiological recordings (patch-clamp) combined with morphological reconstruction of neurons after confocal microscopy in order to correlate the changes in activity with morphological modifications. Modeling will also be used to decipher the relationships between activity and morphology using realistic multi-compartment Hodgkin-Huxley modeling. We propose to study not only mature neurons but also the developmental time course of the electrophysiological phenotype in order to determine when the changes in expression of sodium channels compensating the loss of Nav1.2 occur during development. Our recent results suggest that Nav1.3 subunits may take over the function of Nav1.2 in KO mice. Understanding the role of somatodendritic sodium channels in SNc DA neurons is essential if we want to understand why these neurons degenerate in Parkinson’s disease and whether their vulnerability is a direct consequence of their electrophysiological properties.

The candidate should have a strong knowledge in neurobiology. Experience in biophysics or electrophysiology would be a plus. The data generated by this project are high-dimensional, and some knowledge in multivariate statistical analysis would be also a benefit.

These experiments are covered by the APAFIS project #31844-2021051015363367.