Neural mechanisms of timing in the oculomotor system

描述(由申请人提供)：大脑灵活感知和产生时间间隔的能力是许多认知功能和感觉运动技能的重要组成部分。然而，测量和产生时间间隔的神经机制尚不清楚。我们将利用灵长类动眼系统的解剖学和生理学的基础工作来评估大脑动眼回路中间隔计时的机制。首先，我们将重点放在联合皮质的外侧顶内区(LIP)，在那里已经有过与过去时间相关的报道。我们将从动眼时间复制任务中的嘴唇神经元进行记录，以测试嘴唇反应动力学跟踪动物在测量和产生时间间隔期间对经过时间的估计的假设。其次，我们将使用光遗传学在高时间分辨率下兴奋和抑制LIP中的神经活动，以探讨LIP是否以及如何在时间间隔的感知和产生中发挥因果作用。第三，我们将检查小脑外侧输出节点(即齿状核，DN)的神经信号，该信号被认为在时间和时间协调中发挥重要作用。基于先前提出的外侧小脑在非运动计时中的作用的工作，我们将检验这一假设，即在时间间隔的测量中，DN信号编码逝去的时间。这些实验结合了多种创新，包括新颖的行为范式和尖端技术，有可能为我们理解灵长类大脑中间隔计时的神经机制做出重大贡献。

DESCRIPTION (provided by applicant): The brain's capacity to sense and produce time intervals flexibly is an essential building block of many cognitive functions and sensorimotor skills. Yet, the neural mechanisms for measuring and producing an interval of time are unknown. We will take advantage of the foundational work on the anatomy and physiology of the primate oculomotor system to assess the mechanisms of interval timing in the oculomotor circuits of the brain. First, we will focus on the lateral intraparietal area (LIP) of the associaton cortex, where correlates of elapsed time have been reported previously. We will record from LIP neurons in an oculomotor time reproduction task to test the hypothesis that LIP response dynamics track the animal's estimate of elapsed time during both measurement and production of time intervals. Second, we will use optogenetics to excite and suppress neural activity in LIP at high temporal resolution to ask whether and how LIP plays a causal role in the perception and production of time intervals. Third, we will examine the neural signals at the output node of the lateral cerebellum (i.e., the dentate nucleus, DN), which is thought to play an important role in timing and temporal coordination. Based on previous work suggesting a role for the lateral cerebellum in non-motor timing, we will test the hypothesis that DN signals encode elapsed time during measurement of time intervals. These experiments combine multiple innovations including a novel behavioral paradigm and cutting-edge technology and have the potential to make a significant contribution to our understanding of the neural mechanisms of interval timing in the primate brain.