Arousal and Timekeeping in a Mouse Model of Parkinsonism

项目摘要/摘要 运动障碍，如帕金森氏病(PD)和亨廷顿病， 以计划和执行动作以及认知方面的严重障碍为特征的 赤字，其中一些源于对持续期估计的赤字。估算和复制 秒到分钟范围内的持续时间对于基本过程至关重要，例如 联想学习、有计划的运动反应和决策。该项目将探索 神经生物学机制涉及持续时间的估计和复制 评估帕金森病小鼠模型的计时运动反应缺陷。我们将调查 觉醒，以及一种新的神经递质，食欲素，参与计时的改变 帕金森病患者使用新开发的时序反应选择缺陷模型进行反应选择。 我们还将评估挽救运动计时缺陷的药理学方法。该项目 将加强我们对认知和运动控制的神经元过程的理解 运动障碍的缺陷，并将有助于开发新的动物治疗策略 模型，可能会对临床治疗产生影响。

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.