Sensorimotor integration in mammalian cerebellum

项目摘要/摘要： 推论放电(CD)，或传出运动指令的副本，是许多模型小脑不可或缺的 马达控制。假设CD提供参考信号以更新当前电机的内部模型 陈述和修改由运动命令预测的传入感觉输入，将其置于 传感器马达集成。我们对CD的特殊解剖和生理环路的理解 然而，哺乳动物的小脑是有限的，因为解剖学上的限制使运动研究变得复杂。 皮质来源的CD信号。我们的方法通过专注于一条被忽视的道路来绕过这些障碍 由从运动前核团到小脑颗粒细胞层的侧支组成。这 实验上可获得的“核皮质”通路具有CD通路的所有特征，因为它包括 运动输出神经元也投射到感觉接受区。我们建议调查 这一途径在小鼠体内的组织和功能是了解其机制和作用的一种手段 哺乳动物小脑感觉加工过程中的必然放电。来检验CD和CD的假设 更新内部模型并抑制感觉再传入，我们将使用解剖学和生理学 检查核皮质通路是否形成兴奋性突触至前馈的方法 兴奋性颗粒神经元和前馈抑制性高尔基体神经元。这一安排将提供一个 CD在运动控制中的拟议作用的机制。为了进一步检验CD可以修改的预测 感觉再传入，我们将检查颗粒细胞层的感觉反应是否对 核皮质通路的同时激活或失活。我们预计运动CD通路来自 小脑核团接触颗粒细胞和高尔基细胞，与其他感觉传入小脑汇合， 并通过颗粒细胞层改变感官加工。这些研究将有助于实现我们的长期目标 了解哺乳动物前馈运动控制的电路机制，这对精确 运动障碍，并假设在涉及小脑的运动障碍中受损。

Project Summary/Abstract: Corollary discharge (CD), or a copy of efferent motor commands, is integral to numerous models cerebellar motor control. CD is hypothesized to provide a reference signal to update internal models of current motor state and modify reafferent sensory input that is predicted by the motor command, placing it at the center of sensorimotor integration. Our understanding of the specific anatomical and physiological circuitry of CD in the mammalian cerebellum is limited, however, owing to anatomical constraints that complicate studying motor cortex-derived CD signals. Our approach bypasses these obstacles by focusing on a neglected pathway consisting of collaterals from the premotor cerebellar nuclei to the cerebellar granule cell layer. This experimentally accessible "nucleocortical" pathway has all of the hallmarks of a CD pathway in that it consists of motor output neurons that also project to sensory receptive areas. We propose to investigate the organization and function of this pathway in mice as a means to understand the mechanisms and role of corollary discharge in sensory processing in mammalian cerebellum. To test the hypothesis that CD both updates internal models and suppresses sensory reafference, we will use anatomical and physiological approaches to examine whether the nucleocortical pathway forms excitatory synapses onto feedforward excitatory granule neurons and feedforward inhibitory Golgi neurons. This arrangement would provide a mechanism for the proposed roles of CD in motor control. To further test the prediction that CD can modify sensory reafference, we will examine whether sensory responses in the granule cell layer are sensitive to concurrent activation or inactivation of the nucleocortical pathway. We expect that the motor CD pathway from the cerebellar nuclei contacts granule cells and Golgi cells, converges with other sensory cerebellar afferents, and modifies sensory processing by the granule cell layer. These studies will aid in our long term goal of understanding the circuit mechanisms of feedforward motor control in mammals, which is critical for precise movement and hypothesized to be impaired in movement disorders that involve the cerebellum.