Neural mechanisms of timing in the oculomotor system

描述（由申请人提供）：大脑灵活地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是未知的。我们将利用灵长类动眼肌系统解剖学和生理学的基础工作来评估大脑动眼肌回路中间隔时间的机制。首先，我们将重点关注联合皮层的外侧顶叶内区（LIP），在那里流逝的时间的相关性已被报道。我们将在动眼肌时间复制任务中记录LIP神经元，以验证LIP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，我们将利用光遗传学在高时间分辨率下激发和抑制LIP中的神经活动，以了解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，我们将检查外侧小脑输出节点的神经信号（即齿状核，DN），它被认为在时间和时间协调中起重要作用。基于先前的研究表明外侧小脑在非运动计时中的作用，我们将测试DN信号在测量时间间隔时编码流逝时间的假设。这些实验结合了多种创新，包括一种新的行为范式和尖端技术，并有可能为我们理解灵长类动物大脑间隔时间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.