Context- and phase-dependent gating of cerebellar output

小脑输出的上下文和相位相关门控

• 批准号: 10163693
• 负责人: Jesse I Gilmer
• 金额: $ 3.46万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10163693
• 关键词: Ablation; Affect; Behavior; Behavioral; Brain; Brain Stem; Cell Nucleus; Cephalic; Cerebellum; Complex; Coupled; Dependence; Disease; Forelimb; Functional disorder; Hand; Impairment; Lead; Limb structure; Measures; Mediating; Methods; Midbrain structure; Motor; Motor Pathways; Motor output; Movement; Mus; Muscle; Output; Pharmacology; Phase; Process; Property; Receptor Activation; Red nucleus structure; Research; Rest; Site; Spinal Cord; Structure; System; Testing; Triceps Brachii Muscle; Work; biceps brachii muscle; deltoid muscle; designer receptors exclusively activated by designer drugs; effective intervention; experimental study; in vivo; kinematics; limb movement; motor disorder; optogenetics; outreach; receptor; receptor expression; recruit; relating to nervous system; tool

Project Summary The cerebellum is essential for producing skilled movements, like reaching, and dysfunction of this structure causes disruptive motor disorders. However, how cerebellar output influences the structures that command skilled motor output remains unclear. Cerebellum targets the red nucleus (RN), a brainstem pre-motor nucleus that is known to command movements of the limbs. Previous research in my lab has shown that modest optogenetic activation of the interposed nucleus of the cerebellum (IN) results in a kinematic perturbation of the forelimb in mice performing reaching movements12. Strikingly, the properties of the observed perturbation are context-dependent, but phase-independent, e.g. there is no movement at rest, and the same change in movement occurs both in outreach and return of the paw. These findings lead me to hypothesize that cerebellar output is interpreted differentially downstream depending on context and phase, and that RN is a site that mediates differential effects of cerebella output. To test this hypothesis, I will record neural activity in RN during differing phases of reach and at rest while activating IN optogenetically. This will allow me to examine if IN activation differential effect on RN activity between contexts and phases. Additionally, I will record the activity of muscles of the forelimb during IN activation to determine if the effect on muscle activation is dependent on context and phase. I expect to find that both RN activity and EMG amplitude will be reduced during rest, different between phases, and that the observed changes will aid in explaining the observed context-dependence and phase-invariance. I will also establish the degree of necessity of the cerebellorubral circuit in mediating these effects through the expression of excitatory and inhibitory designer receptors in RN, that, when paired with IN stimulation optogenetically, should reveal the input output relationship between IN, RN, and the effected kinematics due to the cerebellorubral motor pathway.

项目摘要 小脑对于产生熟练的动作是必不可少的，比如伸展和这个结构的功能障碍 会导致破坏性的运动障碍。然而，小脑的输出如何影响命令的结构 熟练的汽车产量仍不明朗。小脑定位于红核(RN)，这是一种脑干运动前核团 这是已知的控制四肢运动的装置。我实验室之前的研究表明， 小脑间隔核(IN)的光遗传激活导致运动扰动 在进行伸展运动的小鼠的前肢。令人惊讶的是，观测到的微扰的性质是 与上下文相关，但与阶段无关，例如，没有静止的运动，并且 运动既发生在爪子的外伸，也发生在爪子的返回。这些发现使我假设 小脑输出根据上下文和时相的不同向下游解释，RN是一种 调节小脑输出的差异效应的站点。为了验证这一假设，我将记录下 RN在到达和静止的不同阶段，同时光遗传地激活IN。这将使我能够 检查IN激活是否对RN活动在上下文和阶段之间存在差异影响。另外，我会 记录在IN激活过程中前肢肌肉的活动，以确定是否对肌肉激活有影响 取决于背景和阶段。我预计会发现RN活动和EMG幅度都会降低 在休息期间，不同阶段的变化是不同的，观察到的变化将有助于解释观察到的 上下文依赖性和相不变性。我还将确定小脑和腰椎的必要性程度 在RN中，通过兴奋性和抑制性设计受体的表达来调节这些效应的回路， 当与IN刺激在光遗传学上配对时，应该揭示IN、 RN，以及由于小脑-腰椎运动通路而影响的运动学。

项目成果

An emergent temporal basis set robustly supports cerebellar time-series learning.

紧急时间基础集有力地支持小脑时间序列学习。

• DOI: 10.1152/jn.00312.2022
• 发表时间: 2023
• 期刊: Journal of neurophysiology
• 影响因子: 2.5
• 作者: Gilmer,JesseI;Farries,MichaelA;Kilpatrick,Zachary;Delis,Ioannis;Cohen,JeremyD;Person,AbigailL
• 通讯作者: Person,AbigailL