The experiments in this proposal are designed to investigate the basis of changes in cognitive flexibility caused by normal aging. Subsets of elderly humans and rats appear to have difficulty changing behaviors when the likely outcomes of those behaviors change. These deficits are evident in tasks that test reversal learning and set-shifting. Reversal learning and set-shifting are critically dependent on two different subdivisions of prefrontal cortex in rats and primates. These circuits are implicated in control of different forms of associative learning. Here we will test the associative basis and circuits involved in these declines in normal aging. Findings will show whether declines in these two types of cognitive flexibility occur independently in the two prefrontal systems or whether they reflect a unitary phenomenon. Associated experiments will identify regional changes in neural activity, dendritic structure, and monoaminergic innervation that correlate with performance changes to identify the location and underlying cause of miscoding associated with the inflexible behavior. Lastly we will test the hypothesis that practice on a task that emphasizes learning in one of these associative domains results in a protective effect on later performance, after aging, within the same associative domain. Improved performance may then be correlated with regional changes in neural activity, dendritic structure and innervation.
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