Boucard Lab

The way we think, form memories or learn, test the ability of our brain to function properly. In order to do so, both the developing brain and adult brain rely on the adequate establishment of specific neuronal networks, each possessing unique properties and functions. Neurons participate in their respective network by establishing specific connections through junctions of 15-25 nanometers called synapses. Described almost a century ago after the invention of electronic microscopy (EM), synapses are composed of two distinct compartments: a) a pre-synaptic side characterized by the presence of vesicles and b) a post-synaptic compartment characterized in excitatory synapses by the presence of electron dense material. Given that synapses constitute the functional units of the brain, understanding the events leading to their formation is of prime importance.

 

The Boucard lab is interested in molecular correlates of synapse formation and function. We focus on a unique set of molecules that are part of the “Adhesion G-protein Coupled receptor” family (aGPCR). These atypical GPCRs possess a long N-termini composed almost exclusively of adhesion motifs known to be mediating protein-protein interactions. However, most of the receptors in this family are considered Orphan Receptors i.e. no endogenous ligands have been characterized. We hypothesize that these adhesion motifs are involved in events leading to synapse formation and function through intermolecular interactions with unknown ligands. We suspect that these interactions procure the specificity of synapse formation and function to neuronal networks.

 

We intend to tackle the Adhesion GPCR-mediated specificity/ functional aspects of synapse formation events by the development of the following platforms of investigation:

 

1. Identification and characterization of potential ligands for aGPCRs using biochemical and cell biology approaches.

 

2. Determination of aGPCRs-mediated cellular pathways using biochemical and cell biology approaches.

 

3. Development of imaging tools to visualize aGPCR-mediated synapse formation using confocal microscopy.

 

4. Analysis of the role of aGPCRs in neuronal physiology using genetically modified mice.

 

We expect to understand how Adhesion-GPCRs contribute to “normal” neuronal functions and what their involvement is in neuropathological conditions like neurodegeneration or neurodevelopmental disorders like Autism and Attention Deficit Disorders.