Les complexes d'adhésion et d'organisation synaptiques : leurs rôles dans le cerveau sain et dans le cerveau malade

 

Hideto Takahashi

Institut de recherches cliniques de Montréal [IRCM]

 

Domaine : neurosciences, santé mentale et toxicomanies

Programme Chercheurs-boursiers - Senior

Concours 2018-2019

My research program aims to understand the mechanisms that influence how brain cell connections called synapses develop for normal brain function (Project 1) and how these synapses become dysfunctional in cognitive disorders such as Alzheimer's disease, schizophrenia, and autism (Project 2). Normal brain function relies on a balance of synapses transmitting excitatory or inhibitory signals between the brain cells termed neurons.

Our recent studies have shown that two proteins, TrkC and IgSF21, selectively promote the development of excitatory and inhibitory synapses, respectively. In Project 1, we are examining the roles of these two proteins in synapse development, synaptic plasticity, and brain activity by using cellular, molecular, electrophysiological, and genetic approaches. In Project 2, we focus on Alzheimer's disease because we have recently discovered that key toxic components causing this pathology, called amyloid-beta oligomers, interact with synaptic adhesion molecules named neurexins and disrupt their function.

Therefore, we are determining how neurexins and their binding partners influence amyloid-beta-induced synaptic pathology using advanced techniques in molecular and cellular biology and electrophysiology. Ultimately, this research program will provide us with an understanding of the molecular mechanisms of synapse development necessary for maintaining the neural excitation/inhibition balance in the brain and also improve our knowledge of the pathological mechanisms of synaptic dysfunction in Alzheimer's disease. Because there are genetic associations of TrkC and neurexins with autism, schizophrenia and anxiety, our results may help develop novel therapeutic strategies to prevent and treat both cognitive impairment and mental illness.