Thesis, COLLÉGIALITÉ

Abstract

Cortical interneurons are cardinal for the correct function of neocortical circuits. A disruption in their neurogenesis, migration, connectivity or circuit maturation might lead to important consequences on the fine excitation-inhibition balance and the debut of developmental disorders such as autism spectrum disorder, epilepsy and schizophrenia. Cortical interneurons are born in the ventral forebrain and interneuron migration is a limiting step for cell integration into the cortical layer and the establishment of neuronal circuits. It is therefore crucial to understand the specific mechanisms of guidance to the cortex. A recent publication shed light on the important role of first-wave oligodendrocyte precursor cells (OPCs) as a support for the migration of interneurons, concomitantly travelling across the cortex. In fact, OPCs perform unidirectional contact repulsion with interneurons mediated by the interaction of semaphorin 6a and plexin A3 receptors to impede their adherence to blood vessels, which release the chemokine Cxcl12. Complete depletion of the first-wave OPCs induced a decrease in the number of interneurons in the cortical wall and their accumulation in the ventral subventricular zone, suggesting the important consequence of this interaction on interneuron speed migration. The goal of this work is to explore the fine mechanisms of interneuron-OPC interaction by preventing the expression of semaphorin 6a and CXCR4 receptor, thereby interfering with their response to Cxcl12. By selectively impairing these signalling pathways we will be able to assert their exclusive role and investigate the post-natal sequelae of interneuron delay in migration.