Neurophysiology of time production

描述(由申请者提供)：这项研究将主要在墨西哥国立大学神经生物学研究所与Hugo Merchant-Nancy合作进行，作为NIH赠款#5R01-NS042778的延伸。间隔计时是一个复杂的过程，它并不完全与任何感觉通道联系在一起，它涉及从物体拦截和碰撞避免到音乐表演和语音的广泛行为。然而，关于时间加工的神经生理学基础的信息明显缺乏。这项研究的目标是了解100-1000ms范围内间隔计时的神经基础，更具体地说，研究皮质-丘脑-基底节回路(CTBG)在这一行为中的作用。尽管许多药理学、损伤和影像研究表明CTBG参与了时间加工，但间期计时的神经机制仍不清楚。我们的总体论点是，时间间隔的产生依赖于内部时钟，其神经生理机制基于整个CTBG中信息的分布式处理。为了测试这些想法，恒河猴将接受训练，进行涉及产生单个或多个时间间隔的任务。在任务执行过程中，将使用7微电极系统记录CTBG的两个结构，即辅助运动区(SMA)和壳核，记录单个细胞的冲动活动。这些数据将使用单变量和多变量统计方法进行分析，以将计时行为与单细胞和群体活动联系起来。这将使我们能够阐明CTBG成分在时间信息处理中的作用，破译神经密码，并揭示间隔计时的机制。

DESCRIPTION (provided by applicant): This research will be done primarily in Mexico at the Institute of Neural Biology, National University of Mexico in collaboration with Hugo Merchant-Nancy as an extension of NIH grant # 5R01-NS042778. Interval timing is a complex process that is not linked exclusively to any sensory modality and that is involved in a broad spectrum of behaviors, ranging from object interception and collision avoidance to musical performance and speech. However, there is a remarkable lack of information regarding the neurophysiological basis of temporal processing. The goal of the work outlined in this proposal is to gain understanding of the neural basis of interval timing in 100--1000 ms scale, and more specifically to investigate the role of the corticothalamic-basal ganglia circuit (CTBG) in this behavior. Although many pharmacological, lesion and imaging studies have implicated CTBG in temporal processing, the neural mechanisms of interval timing are still unknown. Our general thesis is that the production of time intervals depends on an internal clock whose neurophysiological mechanism is based on the distributed processing of information throughout the CTBG. In order to test these ideas, Rhesus monkeys will be trained in tasks that involve the production of single or multiple time intervals. The impulse activity of single cells will be recorded during task performance in 2 structures of the CTBG, namely, the supplementary motor area (SMA) and the putamen using a 7-microelectrode system. The data will be analyzed using uni-and multivariate statistical methods to correlate timing behavior and single cell and population activity. This will allow us to elucidate the role of CTBG components in temporal information processing, decipher the neural codes, and reveal the mechanism of the interval timing.