Neurogenesis in an Animal Model of Cognitive Aging

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The observation that neurogenesis occurs in the adult dentate gyrus has sparked much speculation regarding a role for this phenomenon in hippocampal mnemonic function. This hypothesis may extend to cognitive aging, an idea supported by reports of age-related declines in neurogenesis [2,3,4] and substantial evidence for cognitive deficits during aging in functions that depend on the hippocampal formation [1]. Yet, to date, there is little evidence that changes in the rate of proliferation, survival or differentiation of these newly generated cells has consequences for cognitive function associated with the hippocampus in either young or aged animals. The proposed experiments will directly examine an association between cognitive abilities and neurogenesis in a well characterized model of hippocampal aging. Specifically, young, middle-aged, and aged rats will be behaviorally characterized on the spatial version of the Morris water maze task and a delayed match-to-place task that will assess working memory (Specific Aim 1). These behaviorally characterized rats of different ages then will be evaluated for the rate of proliferation and survival of new cells in the hippocampus (Specific Aim 2). Those results will be compared to data obtained in the olfactory system in the same subjects (Specific Aim 3). Additional material and methods will be used to study the numbers of newly generated hippocampal cells that differentiate into neurons (Specific Aim 4). Each of these aspects of neurogenesis will be related to individual differences in cognitive aging.