Description du sujet de thèse

Understanding how the neurobiological and cognitive disorders of schizophrenia generate clinical symptoms is essential for linking molecular mechanisms to cognitive functions. Schizophrenic patients exhibit alterations in temporal processing, such as difficulty detecting sensory asynchronies or perceiving very short intervals. These deficits are linked to dysfunctions in communication between the prefrontal cortex (PFC) and the cerebellum, regions involved in executive functions and the temporal sequencing of our actions, respectively. For example, the cerebellum predicts the sensory feedback of our actions in order to adjust our movements in anticipation or modify the motor command on the next trial. Miscalculation of these predictions in schizophrenia could transform internal sensations into external stimuli, contributing to hallucinations. This hypothesis is reinforced by studies showing that transcranial magnetic stimulation (rTMS) of the cerebellum can restore cerebello-prefrontal connectivity and alleviate certain symptoms. The project aims to analyze this communication in mice in two models of schizophrenia: a pharmacological model (ketamine) and a genetic model (synapsin II deficiency). By recording neuronal activity during temporal discrimination tasks, the objective is to understand how alterations in synchronization impact performance.
Targeted stimulation of Purkinje cells will allow us to explore the effects on the PFC and test stimulation protocols to correct behavioral deficits.
In collaboration with Anne Giersch's team, this work could refine clinical approaches to cerebellar stimulation by rTMS and pave the way for more effective therapeutic strategies for treating schizophrenia.

Contexte de travail

The doctoral student will work for a period of 36 months in the “Neural Network Physiology” team at the Institute of Cellular and Integrative Neuroscience (INCI – UPR3212), under the supervision of Dr. Philippe Isope. The team consists of approximately 16 people (including 6 permanent researchers) and the INCI has 9 teams in total, for a total of approximately 130 employees, including around fifty permanent researchers. Part of the work, particularly the behavioral aspect, will be carried out at the Chronobiotron (CNRS UAR3415), the animal experimentation platform associated with the INCI.
The CNRS is a leading research institute recognized worldwide for its scientific excellence.
The doctoral student (M/F) will be enrolled in the doctoral school of life and health sciences at the University of Strasbourg (https://ed.vie-sante.unistra.fr).

Contraintes et risques

Working with animals (rodents)