Nervous system function depends on complex networks of interconnected cells. The Kennedy laboratory at McGill’s Montreal Neurological Institute investigates the cellular and molecular mechanisms that underlie the formation, modification and maintenance of the synaptic connections between neurons, and of myelin, the insulating glial sheath around axons, all processes that share in common the precise regulation of cell motility and adhesion. A major and long-term focus of our studies is the netrin family of secreted proteins that direct cell and axon migration during development. Although initially studied for their contribution during embryogenesis, we discovered that these same proteins also regulate synapse formation during early post-natal maturation, synaptic plasticity, learning and memory, and maintenance of myelin in the adult brain. Disruption and loss of synapses is a key component of neurodegenerative disorders like Alzheimer’s and Parkinsons’s disease, while myelin loss is central to demyelinating diseases such as multiple sclerosis. Importantly, recent studies indicate that mutations in the human genes encoding netrins and netrin receptors are correlated with the susceptibility to develop Parkinson's disease, amyotrophic lateral sclerosis, and Alzheimer’s disease. While these proteins are absolutely essential for normal neural development, their significance in the mature brain is only beginning to be appreciated. The tools and expertise developed by the Kennedy lab position us to make groundbreaking discoveries related to how netrins influence critical cell-cell interactions in the central nervous system. Our research aims to identify the biochemical mechanisms that maintain and modify the connections between neural cells, with the ultimate goal of identifying new therapeutic targets to prevent loss of function due to aging or neurodegenerative disease.