Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Many cognitive processes rely on the ability of brain cells (neurons) to adapt electrochemically and structurally, while maintaining stable connections. This plasticity occurs at specialized junctions called synapses - the sites at which neurons communicate. Many studies have examined the plasticity of synapses, but most have focused only on the hippocampus and cortex. Little is known about synaptic plasticity in other important regions, such as the striatum. The striatum is an integrative centre, crucial in guiding behavior by comparing sensory information to past experiences. It receives input from multiple brain areas, and is involved in neuropsychiatric disorders, addiction and neurodegenerative diseases such as Parkinson's disease (PD). PD affects ~2% of individuals > 65 years, and is characterized by impaired movement, emotional disturbances and cognitive decline. Mutations in a gene for a protein called leucine-rich repeat kinase 2 (LRRK2) are the most common risk factor for PD; yet the function of LRRK2 has only recently become a research focus. Our lab has found that this protein plays an important role in synaptic activity, with mutations in it causing an increase in neurotransmitter release and changes in the activity of other synaptic proteins. Thus, examining how LRRK2 affects the morphology and physiology of striatal neurons is important to understanding what role this protein plays in PD. I will first examine how manipulating neuron activity affects synapse formation and maintenance. This work will then be repeated in cells from mice that have the LRRK2 mutations seen in PD to determine the protein's role in regular synaptic function and the potential changes induced by PD-linked mutations. This research is crucial for linking structure and function in order to understand the processes underlying synapse activity and plasticity, and how these may be targeted in new therapeutics for neurodegenerative disorders such as PD.