Venue: Centre Broca Nouvelle-Aquitaine
Defense in english.
Thesis supervisor: Nathalie Sans (Magendie)
Role of the planar polarity pathway in cognitive functions in the context of postnatal development and aging
Lack of knowledge on the mechanisms of development and function of the central nervous system are slowing our efforts to take care of people suffering from cognitive disorders. Understanding those mechanisms and their role in the modification of neuronal and synaptic properties induced by the environment during life and aging is therefore necessary.
My PhD research project tackles this issue through the study of the planar cell polarity protein Vangl2, which is known to regulate cytoskeleton dynamics during development. I study the role of this protein in the hippocampus, a cerebral structure involved in episodic memory and context discrimination, which is known to be affected in some cognitive disorders. Preliminary data from the lab showed that Vangl2 is enriched postnatally in the network formed by 2 sub-regions of the hippocampus: the dentate gyrus and the CA3. My work shows that Vangl2 plays a crucial role in the development and maintenance of a specific synaptic connection in this network: the synapse formed between the granular cell of the DG and the pyramidal neurons of the CA3. Using a mice model for an early deletion of Vangl2 and techniques of virus injections and microscopy, I show that the early loss of Vangl2 delays the development of the synapse and affects its structural plasticity in adults. Using behavioural experiments, I show that the early loss of Vangl2 induces defects in some memory processes involving the hippocampus in adult mice. Interestingly, data in aging mutant mice show that the early loss of Vangl2 in the hippocampus has protective effects against the functional and morphological degradation of the DG/CA3 network linked to aging.
These results show the importance of Vangl2 in the morphofunctional properties of the DG/CA3 network across development and aging and establish a link between the planar cell polarity pathway, the synaptic development and function in the hippocampus, and cognitive processes through life.
Keywords : hippocampus, memory, planar polarity, plasticity, cognitive processes
Pr Marc Landry, Pr. Fadel Tissir, Dr. Claire Rampon, Dr. Nelson Rebola, Dr. Cordelia Imig, Dr. Nathalie Sans