Arousal and Timekeeping in a Mouse Model of Parkinsonism

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PROJECT SUMMARY / ABSTRACT Movement disorders, such as Parkinson’s Disease (PD) and Huntington’s Disease, are characterized by drastic impairments in planning and executing movement, as well as cognitive deficits, some of which stem from deficits in estimating durations. Estimation and reproduction of durations in the seconds-to-minutes range are critical for fundamental processes such as associative learning, planned motor responses and decision-making. This project will explore neurobiological mechanisms involved in the estimation and reproduction of durations to evaluate timed motor response deficits in mouse models of PD. We will investigate the role of arousal, and the involvement of a novel neurotransmitter, orexin, in alterations of timed response selection using a newly developed model of timed response selection deficits in PD. We will also evaluate pharmacological approaches to rescue motor timing deficits. The project will enhance our understanding of neuronal processes involved in cognitive and motor control deficits in movement disorders, and will help develop new treatment strategies in animal models, with possible subsequent impact on clinical treatments.