Neural Encoding of Errors in the Cerebellum

 描述（由申请人提供）：有效的运动控制需要持续监测和纠正错误。虽然最初假设使用感觉反馈来纠正错误，但固有的延迟使控制不充分且不稳定。一种解决方案是CNS实现预测运动命令的感觉后果的前向内部模型（forward internal model，简称NIM）。然后将预测结果与实际感觉结果进行比较，生成用于改进后续预测的感觉预测误差（SPE）。广泛的研究表明，小脑作为一个神经元，但编码SPE的机制是未知的。本研究的总体目标是了解小脑皮层主要输出神经元浦肯野细胞（Purkinje cells，PC）及其在小脑深核（Deep Cerebellar Nucleus，DCN）的投射靶点的错误编码机制。虽然占主导地位的假设是，错误是由低频PC复杂的尖峰（CS）放电编码，从我们的实验室的结果有牵连的简单尖峰（SS）放电的预测和反馈的性能误差信号的处理。许多PC具有运动学和性能误差的双重表示，并且预测和反馈信号对SS具有相反的影响，与SPE一致。此外，与性能误差相关的SS排放在一系列时间尺度上表示（-2000至2000毫秒），这一建议的第一个目的是通过观察与运动错误预测和反馈相关的破坏性感觉信息如何调节PC和DCN活动来研究双重编码的性质，以检验编码代表SPE的预测和反馈组件。第二个目的是研究SS放电在编码运动记忆中的作用。将采用一种新的跟踪模式，需要编码、维护和检索简化的轨迹。该假设是，轨迹的各个方面将被编码的SS放电在每一个三个阶段的范例。这个建议的结果将阐明小脑中与在线运动控制以及运动记忆相关的错误处理背后的细胞机制。

 DESCRIPTION (provided by applicant): Effective motor control requires continuous monitoring and correction of errors. While it was originally postulated that errors are corrected using sensory feedback, the inherent delays render control inadequate and unstable. One solution is that the CNS implements a forward internal model (FIM) that predicts the sensory consequences of motor commands. The predictions are then compared to the actual sensory consequences, generating sensory prediction errors (SPEs) used to improve subsequent predictions. Extensive research suggests that the cerebellum serves as a FIM, but the mechanisms by which SPEs are encoded are unknown. The overall goal of this proposal is to understand the mechanisms of error encoding by the primary output neurons of the cerebellar cortex, Purkinje cells (PCs), as well as their projection targets in the deep cerebellar nuclei (DCN). While the dominant hypothesis is that errors are encoded by the low frequency PC complex spike (CS) discharge, results from our lab have implicated simple spike (SS) discharge in the processing of both prediction and feedback of performance error signals. Many PCs have this dual representation for both kinematics and performance errors, and the prediction and feedback signals have opposing effects on the SS, consistent with an SPE. Further, SS discharge related to performance errors is represented across a range of time scales (-2000 to 2000 ms), suggesting a potential relevance to working memory The first aim of this proposal seeks to investigate the nature of the dual encoding by observing how disrupting sensory information pertinent to motor error prediction and feedback modulates PC and DCN activity in order to test the hypothesis that the encoding represents the predictive and feedback components of an SPE. The second aim of this proposal seeks to investigate the role of SS discharge in encoding motor memories. A new tracking paradigm will be utilized requiring the encoding, maintenance, and retrieval of a simplified trajectory. The hypothesis is that aspects of the trajectory will be encoded by the SS discharge during each of the three stages of the paradigm. The results of this proposal will shed light on the cellular mechanisms behind error processing in the cerebellum relevant to both online motor control as well as motor memory.