INTERVAL TIMING IN MOUSE MODELS OF PARKINSONISM

描述（由申请人提供）：基本的行为凹陷，如联想学习，速率计算和决策，关键依赖于估计和再现的时间间隔在秒到分钟的范围内，间隔计时。这些过程在帕金森病和亨廷顿病、抑郁症、创伤后应激障碍、精神分裂症和成瘾症中被破坏。帕金森病（Parkinson's disease，PD）是第二常见的神经退行性疾病。PD的特点是在计划和执行运动以及认知缺陷，其中一些可能与赤字估计持续时间的严重损害。本申请旨在评估帕金森氏症小鼠模型中的时间缺陷，以了解持续时间的感知、估计和再现以及定时行为反应中涉及的神经生物学机制，并通过药理学操作挽救时间缺陷。我们的研究将有助于阐明 以及与间隔计时行为有关的皮层回路。如果成功，本项目将建立一个敏感的行为任务，可用于早期PD诊断和筛选新的PD动物模型，将在使用现有PD药物的帕金森病小鼠模型中验证该任务，并将评估替代治疗药物在挽救时间方面的效率。 当在特定脑部位全身或局部施用时，小鼠模型中的缺陷。总之，该项目将增强我们对运动障碍中认知和运动控制缺陷所涉及的神经回路的理解，并将有助于在动物模型中开发新的治疗策略，并对临床治疗产生后续影响。

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.