La plasticité synaptique et la neurophysiologie chez les personnes présentant des anomalies des chromosomes sexuels: à la recherche d'un marqueur neurophysiologique du trouble du spectre autistique

 

Jean-François Lepage

Centre de recherche du Centre hospitalier universitaire de Sherbrooke (CHUS)

 

Domaine : neurosciences, santé mentale et toxicomanies

Programme chercheurs-boursiers - Junior 1

Concours 2016-2017

Autistic spectrum disorder (ASD) is a common disease characterized by social deficits and the presence of restricted interests. Although the neurophysiological mechanisms underlying the TSA remain to be clarified, converging data suggests that abnormal synaptic plasticity processes could be central to the pathophysiology of ASD. However, the study of ASD on the sole basis of the clinical phenotype makes difficult the discovery of neurophysiological abnormalities. Indeed, ASD encompasses various disorders, plausibly caused by different mechanisms (eg. Hypo-plasticity vs hyper-plasticity), but with similar consequences on the clinical phenotype.

A promising approach to study the neurophysiological bases of the ASD is to study homogeneous subgroups defined on a common genetic basis. This would allow to determine the precise contribution of genetic factors on synaptic plasticity and brain connectivity. Focusing on the X chromosome, we propose to study synaptic plasticity, morphology and brain connectivity, in relationship with the clinical phenotype, in three clinical populations with socio-cognitive disorders highly reminiscent of ASD: The Fragile-X syndrome (FXS), Turner syndrome (ST) and Klinefelter syndrome (KS).

Overall, my research program aims to test the hypothesis, in humans, that ASD disorder characterized by aberrant synaptic plasticity mechanisms. To do this, I will use transcranial magnetic stimulation and magnetic resonance imaging to document the presence of neurophysiological abnormalities in individuals with FXS, ST, and KS, who are at high risk of ASD.