This project's goal is to develop a nonhuman primate model of learning and memory dysfunction in normal aging. Using CRPRC's population of aged rhesus monkeys, it is anticipated that ~55 subjects 19-30+ years of age will be behaviorally tested over the course of the project. Younger subjects at 4-6 years of age will serve as controls. These investigations aim to develop new learning and memory tasks for monkeys specifically designed to study the relatively subtle deficits associated with normal aging. One ongoing experiment has evaluated spatial working memory in young and aged monkeys using a large octagonal open field maze containing 8 reward locations distributed evenly around the perimeter of the apparatus. This testing requires subjects to learn to visit each location once per trial without returning to locations chosen earlier in the session. Similar to parallel studies in rats, our preliminary results indicate that a majority of young monkeys learn this task rapidly, typically requiring <20 trials to achieve a stringent performance criterion. Although a formal analysis is premature, it is clear that many of these monkeys are able to achieve asymptotic levels of accuracy similar to young monkeys. For a substantial number of aged individuals, however, accurate performance appears to be supported by alternate strategies not seen in younger animals such as visiting reward locations in a fixed sequence across trials. A disproportionate reliance on non-spatial task solutions is a prominent feature of aging in rats; our early results suggest that this effect may generalize to the nonhuman primate model. Considerable progress has also been realized in establishing procedures to evaluate other features of spatial learning and memory in monkeys including forgetting rates, and acquisition and retention in a reference memory version of testing. Our expectation is that such task manipulations will prove particularly sensitive to hippocampal damage, providing valuable tools for examining the functional consequences of subtle neural alterations associated with normal aging. Ultimately, the availability of new procedures sensitive to cognitive aging should facilitate the development of treatments for age-related disorders in which memory is prominently affected.
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