Grant: Master's Award: Canada Graduate Scholarships

Brain cells communicate with each other through synapses. When we form memories, the synaptic connection between cells is strengthened. One cell releases a chemical which can act on the next. Once released, these chemicals must be rapidly cleared in order to maintain effective communication. The most common chemical released in the brain is glutamate, which can strengthen or impair synaptic connections based on its temporal dynamics; if glutamate is not rapidly cleared, it will prevent the strengthening of the synaptic connections. Alzheimer Disease (AD) is the most common neurodegenerative disease characterized by debilitating cognitive impairments. Contributing to memory impairments, a toxic protein termed amyloid beta (A?) builds up in the AD brain. It is widely accepted that A? impairs memory by preventing the rapid clearance of glutamate following release. However, these studies used indirect methods to reach their conclusions, and were unable to measure glutamate dynamics in real-time. I have generated strong preliminary data demonstrating that A? does not affect glutamate clearance despite its effects on the strength of synaptic connections. My research will use a novel optical approach to fully characterize the A? effect, or lack thereof, on glutamate dynamics in relation to the strength of synaptic connections in the brain. I will also attempt to restore A?-mediated impairments by increasing glutamate clearance. As my preliminary data strongly argues against a popular view of AD pathology, further investigation into the mechanisms of A?-induced impairments is required to gain a better understanding of the neurobiology of AD, and will help guide the development of novel therapeutics for treating this devastating disease.