The thriving and survival of humans, as well as other species fundamentally depends on the ability to rapidly adapt to changing environmental contingencies. The long-term objective is to understand the brain circuitry that facilitates the learning of new rules with exposure to changing conditions. Huntington's and Parkinson's disease are marked by cellular alterations in the striatum and patients with these diseases exhibit deficits in cognitive flexibility. These findings suggest that the striatum is one brain area that may play a central role in cognitive flexibility. However, the striatum is made up of different subregions possibly subserving different cognitive and behavioral functions. Understanding whether particular striatal subregions facilitate the learning and flexible use of behavior-guiding rules, e.g. switiching strategies, will lend important insight into the neurobiology of learning and behavior flexibility. Ultimately, information obtained on the neurocircuitry underlying behavioral flexibility may enable the development of effective treatments for alleviating the cognitive symptomology observed in patients with Huntington's and Parkinson's disease. The present proposal examines whether the dorsomedial striatum in rats is involved in different forms of behavioral flexibility. In a related group of experiments, the effect of dorsomedial striatal inactivation on the learning and reversal of visual cue and turn discrimination rules are evaluated. Specific to behavioral flexibility, these experiments will examine whether dorsomedial striatal inactivation impairs learning when rats have to shift within a dimension (intra-dimensional shift), e.g. shift from a left turn rule to a right turn rule, or between a dimension (extra-dimension shift), e.g. shift from a visual cue rule to a turn rule. Overall, the findings from the proposed studies can increase the present knowledge about the brain circuitry underlying learning and behavioral flexibility.
