Cortico-cerebellar interactions underlying motor planning and movement

摘要 神经科学的一个中心目标是了解神经回路如何引起行为。持续和斜坡 额叶皮层的准备活动预测特定的未来运动。准备活动是神经活动， 与引起意志运动的运动计划相关。据推测，筹备活动的目的是 这种活动是由分布在多个大脑区域的过程产生的，但目前还不清楚这种活动是如何介导的。 多区域的相互作用以及哪些大脑区域参与其中。在以前的工作中，我们已经确定了一个 小鼠额叶皮层的离散部分（前外侧运动皮层，ALM）是运动规划的中枢。大 部分ALM神经元显示出对特定未来运动的选择性准备活动。我们最近的数据 表明ALM中准备活动依赖于小脑。ALM和小脑中的神经元 在运动规划过程中做出强烈反应，并对行为做出因果贡献。解剖痕迹显示- 比如这两个大脑区域之间的相互连接。本提案旨在阐明运动如何 由皮质-小脑多区域回路制备。我们的核心假设是小脑 通过控制丘脑皮层的持续活动来调节运动选择性皮层准备活动 通过类似于电机控制的反馈控制计算循环。探讨的具体作用 在运动计划的皮质-小脑相互作用，我们将记录准备活动，同时操纵神经 皮质-小脑回路不同阶段的信号。在aim 1中，我们将识别 皮质-小脑环通过映射小脑皮质中的准备活动来介导运动规划， 原子核。我们假设小脑顶核和它的输入浦肯野细胞选择性地参与规划 定向舔（与ALM一起）。在目标2中，我们将阐明在整个皮质内传播的神经信号- 通过记录和操纵中继脑区域、脑桥核和小脑环中的活动， 丘脑和下橄榄在aim 3中，我们将消除电路节点的具体功能的歧义， 皮质-小脑环路的沉默活动在小脑环路的各个阶段，并确定其 对筹备活动的影响。结果将澄清筹备活动的电路机制，这是一个 一种持续的神经活动形式，是许多核心认知功能的基础。

Abstract A central goal in neuroscience is to understand how neural circuits give rise to behavior. Persistent and ramping preparatory activity in frontal cortex anticipates specific future movements. Preparatory activity is the neural correlate of motor planning that gives rise to volitional movements. Preparatory activity has been postulated to emerge from processes distributed across multiple brain regions, but it is unclear how this activity is mediated by multi-regional interactions and which brain areas are involved. In previous work, we have determined a discrete part of the mouse frontal cortex (anterior lateral motor cortex, ALM) is a hub for motor planning. A large fraction of ALM neurons display preparatory activity selective for specific future movements. Our recent data show that preparatory activity in ALM is dependent on the cerebellum. Neurons in both ALM and cerebellum respond robustly during motor planning and causally contribute to the behavior. Anatomical tracings reveal loop- like reciprocal connectivity between these two brain regions. This proposal aims to elucidate how movements are prepared by the cortico-cerebellar multi-regional circuits. Our central hypothesis is that the cerebellum mediates movement-selective cortical preparatory activity by controlling persistent activity in thalamocortical loops through feedback control computations that are analogous to motor control. To probe the specific roles of cortico-cerebellar interactions in motor planning, we will record preparatory activity while manipulating neural signals at various stages of the cortico-cerebellar loop. In aim 1, we will identify the cerebellar nodes of the cortico-cerebellar loop mediating motor planning by mapping preparatory activity in the cerebellar cortex and nuclei. We hypothesize that the fastigial nucleus and its input Purkinje cells are selectively engaged in planning directional licking (together with ALM). In aim 2, we will clarify neural signals propagating within the entire cortico- cerebellar loop by recording and manipulating activity in the relay brain regions, the pontine nucleus and the thalamus, as well as the inferior olive. In aim 3, we will disambiguate the specific functions of circuit nodes within the cortico-cerebellar loop by silencing activity in various stages of the cerebellar loop and determine their impacts on preparatory activity. The outcome will clarify circuit mechanisms of preparatory activity, which is an form of persistent neural activity underlying many core cognitive functions.