Job ID: 106508
PhD project – Identifying early signs of circuit dysfunction before epilepsy onset in murine models of cortical malformations
Position: Ph.D. Student
Deadline: 2 April 2023
Employment Start Date: 2 October 2023
Contract Length: 3 years
Institution: Aix Marseille Université
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
Epilepsies are progressive brain network disorders, and especially those arising in childhood as a consequence of malformations of cortical development (MCDs). Seizures are known to result from abnormal circuit activity; however, circuit-level changes that progressively “render epileptic” developing brains with MCDs remain poorly understood. It is equally unclear how MCDs could interfere with the proper wiring of cortical circuits, and whether signs of circuit dysfunction could be detected at early pre-epileptic stages before epilepsy onset.
Neuroimaging studies in patients with MCDs have highlighted the presence of widespread circuit-level defects extending beyond the macroscopically visible malformation. Through studying murine models of MCDs, the present project aims at identifying and characterizing these early circuit changes, and evaluating their potential impact for cortical operation.
in vivo and in vitro electrophysiological and functional imaging approaches; histology and morphometric methods; in vivo genetic manipulations to induce MCDs (in utero electroporation); in vivo stereotactic injection of viral vectors to express fluorescent reporters or activity sensors.
This project has the ambition to identify early circuit changes, detectable at early pre-symptomatic stages prior to epilepsy onset, and that may serve as biomarkers or predictors of epilepsy outcomes.
3 murine models with cortical malformations; equipped in vivo setups for head-fixed and freely moving recordings; in-house in vivo imaging facility; project authorization for animal research (APAFIS#26835-2020080610441911 v2); ongoing local and international collaborations.
Expected candidate profile
Prior experience with rodent handling and surgeries; in vivo recordings including electrode preparation and stereotactic implantation; stereotactic viral injections; histology and microscopy; data analysis