INTERVAL TIMING IN MOUSE MODELS OF PARKINSONISM

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DESCRIPTION (provided by applicant): Fundamental behavioral recesses such as associative learning, rate calculation and decision-making crucially rely on estimation and reproduction of time intervals in the seconds-to-minutes range, interval timing. These processes are disrupted in Parkinson's and Huntington's diseases, Depression, Post-Traumatic Stress Disorder, Schizophrenia and Addiction. Parkinson's disease (PD) is the second most common neurodegenerative disease. PD is characterized by drastic impairments in planning and executing movement as well as cognitive deficits, some of which may be related to deficits in estimating durations. This application aims at evaluating timing deficits in mouse models of Parkinsonism in order to understand the neurobiological mechanisms involved in the perception, estimation and reproduction of durations, and in timed behavioral responses, and to rescue timing deficits through pharmacological manipulations. Our studies will help elucidate the striatal and cortical circuits involved in interval timing behavior. If successful, this project will establsh a sensitive behavioral task which could be used for early PD diagnosis and for screening for new animal models of PD, will validate this task in a mouse model of Parkinsonism using current PD medication, and will evaluate the efficiency of alternative therapeutical agents in rescuing timing deficits in mouse models when administered systemically or locally in specific brain sites. In summary, the project will enhance our understanding of neural circuits involved in cognitive and motor control deficits in movement disorders, and will help develop new treatment strategies in animal models with subsequent impact on clinical treatments.