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Yann HumeauInstitut interdisciplinaire de neuroscience (IINS) - CNRS / Université de Bordeaux

ATIP-Avenir
Rôle de la plasticité synaptique dans le processus de mémorisation.

Mes recherches

My main objective is to understand the link between synapse and cognition by manipulating synaptic function in behaving mice. The synaptic analysis is performed in vivo and ex vivo using “state of the art” imaging, electrophysiological and behavioral techniques. During my PhD thesis at Strasbourg University, under the supervision of Dr. Bernard Poulain, I was trained in electrophysiology, studying molecular and dynamic aspects of presynaptic plasticity. Then, in Andreas Luthi’s lab in Basel (Switzerland), I worked on amygdala physiology in a context of aversive learning, before returning in Strasbourg as a CNRS researcher in 2005. There, I started the “Syn-IQ” project using genetic mouse models recapitulating human intellectual disorders/syndromes. However, the project fully developed after my moving to Bordeaux in 2010 with the support of the ATIP-Avenir program. Since then, my team entitled “synapse in cognition” aim at deciphering the role of certain forms of synaptic plasticity in behavioral adaptations. At the behavioral level, we are interested by cognitive modalities such as learning, consolidation, flexibility, perseveration and the use of deliberative and procedural strategies.

Mon projet ATIP-Avenir

Neuronal and synaptic physiology in mouse models of mental retardation

Among mental disorders, mental retardation (MR), which concern 1-3% of the general population, has been shown to be caused by various factors including a large array of genetic mutations. Interestingly, over the last 20 years, about 60 X-linked MR genes have been identified. Paradoxically, MR pathophysiology remains largely unknown. In the majority of MR brains, no major alteration of cerebral structure is observed, but when analysed, neuronal networks are often less complex at cellular and synaptic levels. With the exception of transcription and chromatin-remodelling factors, it is worth noticing that most of the MR-related proteins are enriched at pre- and/or postsynaptic compartments. Thus, on the basis of recurrent defects in synaptic function and morphogenesis of dendritic spines, a “synaptic” hypothesis of MR has been proposed.

 The aim of the project is to test this “synaptic” hypothesis by extensively examining synaptic function in MR mouse models. We will particularly focus on several unanswered questions:

  • 1.     the existence of a “functional signature” at synapses of MR mouse models,
  • 2.     the role of MR-related proteins in neuronal network development,
  • 3.     the extent of endogenous compensations mechanisms,
  • 4.     the possibility of phenotypical correction.