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

The brain is comprised of complex neuronal connections with each individual neuron having the capacity to communicate with each other. Neurons possess specialized processes called axons and dendrites. One type of common connection formed on dendrites is called a dendritic spine. Spines are specialized structures in the brain containing many proteins important for contact initiation, neuronal signaling and maturation. These proteins are concentrated in a region of the spine called the postsynaptic density (PSD). One theory is that neurons communicate with each other by initiating contacts using specialized structures called filopodia. Later in development, these long tentacle-like filopodia, are thought to transform into dendritic spines. Paralemmin-1 is a neuronal protein found lining the plasma membrane of dendritic spines. Previous work has shown that a specific amino acid sequence is important for the formation of filopodia in kidney cells. One aspect of my work focuses on how neurons initiate contact formation using filopodia and what proteins are required to drive these filopodia to transform into dendritic spines. Another aspect of my work is to examine how paralemmin-1 and shank1b, a potent spine inducer, can affect spine formation and structure when stimulated with activity. The use of pharmacological agents to stimulate neurons, allows researchers to study proteins and their function under physiological conditions. In my research, I provide stimulation paradigms resembling physiological conditions to deduce whether changes in neuronal morphology can occur. This work is important because deficiencies in dendritic spines can be linked to neurological disorders such as autism and schizophrenia. Also, people with Down's Syndrome show aberrant learning behavior which is correlated with poorly developed dendritic spines. My research will inevitably lead to a better understanding of these diseases and ultimately, to the development of effective treatments.