Développement des circuits neuronaux

 

Edward Ruthazer

Université McGill

 

Domaine : neurosciences, santé mentale et toxicomanies

Programme  Chaires de recherche

Concours 2015-2016

Healthy brain development relies on the proper interaction of genetic and environmental factors.  Sensory experience and neural activity, in particular, are known to play key roles in the essential fine-tuning of functional circuits in the developing brain.  Defects in the activity-dependendent refinement of neuronal connectivity have been directly linked to neurodevelopment disorders like schizophrenia and autism spectrum disorders.  Our work aims to furnish a detailed characterization of the molecular and cellular mechanisms that mediate proper activity-dependent structural and functional circuit refinement.  Only by fully understanding how this phenomenon works in the healthy brain, can we understand and intervene when it goes wrong in neurological disease.

Our experimental approach is to use and to innovate state-of-the-art imaging and electrophysiological techniques that permit us to monitor, over time scales that range from seconds to weeks, how individual neurons modify and refine their synaptic connectivity in the intact animal.  By combining single-cell genetic manipulations with in vivo imaging and recordings to measure how these cells respond to a range of sensory stimuli and neural activity patterns, our goal is to extract a comprehensive set of rules that govern experience-dependent brain circuit refinement and plasticity.  We are systematically testing molecular and cellular participants in this process.  One promising direction has been to explore interactions between neurons and the glial cells that surround them which were once throughout to serve a purely subordinate role.  Our work shows that glial cells actually play a much more fundamental and interactive role in the refinement of developing brain circuits, and therefore are likely of direct relevance in neuropsychiatric disease.  Our long-term goal is to have a much more complete understanding of the contributions of all the relevant players in the process of healthy brain circuit formation to direct future therapeutic intervention.