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是如何引起行为的。持之以恒，勇往直前 额叶皮质的准备活动预测特定的未来运动。准备活动是神经 产生意志性运动的运动计划的关联性。筹备活动已被推定为 从分布在多个大脑区域的过程中出现，但尚不清楚这种活动是如何调节的 通过多个区域的相互作用以及涉及哪些脑区。在以前的工作中，我们已经确定了一个 小鼠额叶皮质的离散部分(前外侧运动皮质，ALM)是运动规划的中枢。大号 部分ALM神经元表现出对特定未来运动有选择性的准备活动。我们最近的数据 表明ALM的准备活动依赖于小脑。ALM和小脑的神经元 在运动计划期间做出强有力的反应，并对行为做出因果贡献。解剖痕迹显示环路- 就像这两个大脑区域之间的相互连接。这项提议旨在阐明运动如何 是由皮质-小脑多区域环路准备的。我们的中心假设是小脑 通过控制丘脑皮质的持续活动来调节运动选择性皮质准备活动 循环通过类似于电机控制的反馈控制计算。探讨……的具体作用 运动规划中皮质-小脑的相互作用，我们将在操作神经的同时记录准备活动 皮质-小脑环不同阶段的信号。在目标1中，我们将识别 皮质-小脑环通过标测小脑皮质和大脑皮质的准备活动来调节运动计划 原子核。我们假设顶核及其输入的浦肯野细胞选择性地参与了计划 定向舔(与ALM一起)。在目标2中，我们将阐明神经信号在整个皮质内的传播。 通过记录和操纵中继区、桥核和大脑中脑区的活动形成小脑环。 丘脑，以及下层橄榄。在目标3中，我们将澄清内部电路节点的具体功能 通过沉默小脑环不同阶段的活动来检测皮质-小脑环，并确定其 对筹备活动的影响。结果将澄清筹备活动的巡回机制，这是一种 作为许多核心认知功能基础的持续性神经活动的形式。

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.