Bidirectional Structural and Functional Plasticity in the Aging Brain.

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The process of aging can negatively impact an individual's cognitive capacity, however there is significant variability across individuals and the reasons for this are the subject of debate. We propose to look at how exercise can impact two theoretical concepts, cognitive capacity and cognitive reserve, in the aged brain. Cognitive capacity is a term that refers to the mechanisms that underlie how we learn, remember and problem solve, and can be assessed using either behavioral tests or electrophysiological analyses. Cognitive reserve is used to describe factors that optimize or promote neurological resiliency in the aged brain, helping to promote higher levels of cognitive functioning. It has been proposed that increases in brain structure may enhance cognitive reserve.***There is considerable evidence that exercise can improve both cognitive capacity and cognitive reserve, however the mechanisms responsible for the benefits of exercise remain to be fully elucidated. In these experiments we will determine if early exposure to exercise is more effective than late exposure to exercise in enhancing cognitive capacity and reserve, or whether life-long exposure is needed. These experiments will utilize multiple experimental approaches (electrophysiological, immunohistochemical, biochemical, behavioral) to develop convergent evidence for the roles structural and functional changes play in optimizing cognitive capacity and cognitive reserve in the aging brain. ***The long-term objective of my research my research program will be to understand how exercise at different time points during development impacts different measures of brain plasticity in the male and female brain and how this relates to learning and memory processes across the lifespan. ***The short-term objectives specific to this research proposal are to: (1) determine whether early life experience is necessary for enhanced cognitive functioning in the aged brain, a way of indexing cognitive reserve; (2) determine whether increased activity in aged populations can have the same benefits, or (3) whether life-long exposure to exercise is required to optimize cognitive reserve. ***To examine these objectives we will employ several novel approaches that we propose can help us differentiate between cognitive capacity and cognitive reserve in the aged brain. Among these will be the introduction a modified rabies virus-mediated tracing system to examine the innervation of dentate granule cells in the aged brain, taking into account whether they were generated early in life (developmental neurogenesis) or later on in adulthood (adult neurogenesis). This will allow us to determine if enhanced neurogenesis early in life enhances cognitive reserve, and produces a population of neurons that can be used in the aged brain to enhance cognitive capacity on demand.