Research

Cellular and molecular mechanisms that support learning and memory

Greenspine laboratory

We want to learn more about the fundamental mechanisms that support learning and memory. We focus on the molecular mechanisms that control synaptic remodeling and the maintenance and modifications of brain circuit connectivity. Synaptic remodelling in the brain during development and in adult life is thought to represent fundamental cellular processes of learning and memory. However, upon abnormal levels of neural activities, it can lead to severe cognitive deficits. The fine line between the mechanisms that produce constructive versus destructive changes in brain circuit connectivity is largely unknown.

To study how synaptic remodeling is regulated, we focus primarily on signaling pathways at excitatory synapses, which are formed on dendritic spines. The methods we use are largely based on neurophotonics, electrophysiology, biochemistry and molecular biology.  

We focus on the spatial dynamics and interactions of glutamate receptors (NMDA and AMPA), signaling proteins (CaMKII, netrin) and structural proteins (PSD95, actin, tubulin) that support synaptic plasticity. We combine functional imaging (Ca2+, voltage), optical imaging of fluorescently-tagged proteins, single molecule imaging, fluorescence nanoscopy (STED, PALM), fluorescence lifetime imaging (FLIM) and Forster resonance energy transfer (FRET), patch clamp electrophysiology, biochemistry and molecular biology.

Several genes and proteins that we study are implicated in brain diseases leading to cognitive, psychiatric or neurodegenerative disorders. 

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Role of the gut microbiota on brain circuit development

Intestinal microorganisms hosted by humans and other vertebrates play a crucial role in maintaining their hosts in healthy conditions. Alterations in the gut microbiota can impact strongly on brain function and mental health, but the underlying mechanisms are poorly understood. To learn more about these mechanisms, we are using a larval zebrafish model in which we control the gut microbiota by various means and observe brain development and function with optical imaging. We aim to use this model to understand the bi-directional modes of communication between the brain and the gut microbiota. 

We take advantage of the transparency of the brain in these larval zebrafish and of several transgenic lines expressing fluorescent proteins or sensors in specific cell types or circuits (obtained from Pierre Drapeau [U Montreal], Ed Ruthazer [McGill U], Marc Ekker [U Ottawa], and Misha Ahrens [Janelia]). 

This project is funded by the Sentinel North initiative. We collaborate with microbiologists, biologists, physicists, mathematicians and engineers at ULaval and CERVO on this project:  Sylvain Moineau, Marie-Eve Paquet, Daniel Côté, Alex Culley, Arnaud Droit, Nicolas Derome, Grant Vandenberg, Simon Hardy, Patrick Desrosiers, and Nicolas Doyon. 

Funding

Our research endeavors are made possible by the following agencies:

Canadian Institutes of Health Research - Instituts de recherche en santé du Canada Fonds de recherche du Québec – Nature et technologies (FRQNT)Fonds de la recherche en santé du Québec  Natural Sciences and Engineering Research Council of Canada (NSERC) - Conseil de recherche en sciences naturelles et en génie du Canada (CRSNG)innovation.caHuman Frontier Science ProgramCanada First Research Excellence FundSentinelle Nord