Cortico-cerebellar interactions underlying motor planning and movement

运动规划和运动背后的皮质-小脑相互作用

• 批准号: 10656397
• 负责人: Nuo Li
• 金额: $ 35万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10656397
• 关键词: Affect; Anatomy; Anterior; Area; Behavior; Behavioral; Brain; Brain region; Cell Nucleus; Cerebellar Cortex; Cerebellar Nuclei; Cerebellum; Clinical; Cognitive; Data; Decision Making; Dimensions; Dissection; Exhibits; Feedback; Future; Gestures; Goals; Inferior; Intervention; Lateral; Lesion; Location; Maintenance; Maps; Mediating; Motor; Motor Cortex; Movement; Movement Disorders; Mus; Nerve Degeneration; Neuroanatomy; Neurons; Neurosciences; Normal Range; Nucleus fastigii; Olives - dietary; Outcome; Output; Play; Pontine structure; Population; Process; Purkinje Cells; Ramp; Reflex action; Research; Role; Short-Term Memory; Signal Transduction; Speech; Stroke; Thalamic structure; Well in self; Work; anatomical tracing; cognitive function; disability; experimental study; frontal lobe; granule cell; motor control; neural; neural circuit; neural correlate; neurotransmission; response; sensory discrimination; skills; social

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.

抽象的 神经科学的一个中心目标是了解神经回路如何产生行为。持续且渐增 额叶皮层的准备活动预测未来的具体动作。准备活动是神经 与引起意志运动的运动规划相关。准备活动预计为 来自分布在多个大脑区域的过程，但尚不清楚这种活动是如何介导的 通过多区域相互作用以及涉及哪些大脑区域。在之前的工作中，我们已经确定了 小鼠额叶皮层的离散部分（前外侧运动皮层，ALM）是运动规划的枢纽。一个大 部分 ALM 神经元表现出针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 的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有力的反应并对行为做出因果贡献。解剖追踪揭示了循环 就像这两个大脑区域之间的相互连接一样。该提案旨在阐明运动如何 由皮质小脑多区域回路准备。我们的中心假设是小脑 通过控制丘脑皮质的持续活动来介导运动选择性皮质准备活动 通过类似于电机控制的反馈控制计算进行循环。探究具体角色 运动规划中的皮质-小脑相互作用，我们将记录准备活动，同时操纵神经 皮质小脑环路各个阶段的信号。在目标 1 中，我们将识别小脑节点 皮质小脑环通过映射小脑皮层的准备活动来介导运动规划 原子核。我们假设顶核及其输入浦肯野细胞选择性地参与规划 定向舔舐（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、脑桥核和大脑中的活动来控制小脑环 丘脑，以及下橄榄。在目标 3 中，我们将消除内部电路节点的具体功能的歧义。 通过沉默小脑环各个阶段的活动来抑制皮质小脑环，并确定其 对准备活动的影响。结果将阐明准备活动的循环机制，这是一个 许多核心认知功能背后的持久神经活动形式。

项目成果

Cortico-cerebellar interactions during goal-directed behavior.

• DOI: 10.1016/j.conb.2020.08.010
• 发表时间: 2020-12
• 期刊: Current opinion in neurobiology
• 影响因子: 5.7
• 作者: Li N;Mrsic-Flogel TD
• 通讯作者: Mrsic-Flogel TD

A midbrain-thalamus-cortex circuit reorganizes cortical dynamics to initiate movement.

• DOI: 10.1016/j.cell.2022.02.006
• 发表时间: 2022-03-17
• 期刊: Cell
• 影响因子: 64.5
• 作者: Inagaki HK;Chen S;Ridder MC;Sah P;Li N;Yang Z;Hasanbegovic H;Gao Z;Gerfen CR;Svoboda K
• 通讯作者: Svoboda K