The role of cerebellar output in the control of motor coordination

小脑输出在运动协调控制中的作用

• 批准号: 10601599
• 负责人: Courtney I Dobrott
• 金额: $ 3.59万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2026-07-22
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10601599
• 关键词: Acceleration; Address; Anterior; Automobile Driving; Behavior; Behavioral; Behavioral Paradigm; Cell Nucleus; Cerebellum; Code; Compensation; Complex; Computer Models; Conditioned Stimulus; Deceleration; Development; Disease; Drops; Dysmetria; Electrophysiology (science); Ensure; Exhibits; Feedback; Forelimb; Generations; Goals; Individual; Knowledge; Laboratory Finding; Learning; Lesion; Limb structure; Location; Maps; Modeling; Motor; Motor output; Movement; Movement Disorders; Mus; Neurons; Output; Patients; Policies; Positioning Attribute; Production; Role; Sensory; Shapes; Signal Transduction; Structure; Testing; Travel; Work; cell type; experimental study; extracellular; in vivo; insight; kinematics; limb movement; motor control; motor learning; neural; novel; novel therapeutics; optogenetics; sensorimotor control mechanism; sensory feedback; skills

Project Summary Individuals with damage to the cerebellum exhibit debilitating deficits in motor coordination, characterized by oscillatory movements around an endpoint. The anterior interposed nucleus (IntA) is one of the main output structures from the cerebellum, with inactivation of IntA resulting in dysmetria and an instability of reaching movements. Recent findings from the lab have revealed the role of IntA as a controller of reach endpoints, facilitating precise limb movements through adaptive scaling of firing rate. While considerable progress has been made in understanding the role of the cerebellum in motor control, many questions remain concerning the signals encoded within IntA neurons during limb movement and how they contribute to the production of coordinated movements. Investigating the firing rate code of IntA neurons during complex motor tasks will help to elucidate the role of the cerebellum in anticipatory control and motor learning. To address this gap in knowledge, this proposal utilizes novel behavioral paradigms for skilled reaching in mice, cell type specific in vivo recordings during behavior, and causal optogenetic manipulations of cerebellar output. I will first determine how IntA activity is modulated to ensure endpoint precision to different targets. To do so, I will examine IntA neural dynamics, both in magnitude and timing, and their relationship to key kinematic parameters of reach precision. Secondly, I will test whether the anticipatory control signals of IntA can adapt to account for reach perturbations. Spanning circuit and behavioral levels, this proposal aims to understand the role of cerebellar output in anticipatory motor control for coordinated movement.

项目摘要 小脑受损的个体在运动协调方面表现出衰弱的缺陷，其特征是 围绕一个端点的振荡运动。前间隔核(INTA)是主要的输出之一 来自小脑的结构，INTA失活导致宫缩困难和伸展不稳 动静。实验室的最新发现揭示了INTA作为REACH端点的控制器的作用， 通过自适应调整射击率，促进肢体的精确运动。虽然取得了相当大的进展，但 尽管在理解小脑在运动控制中的作用方面已经取得了进展，但仍有许多问题值得关注 肢体运动时INTA神经元内编码的信号以及它们如何参与产生 协调动作。研究复杂运动任务中INTA神经元的放电频率编码将有所帮助 目的：阐明小脑在预期控制和运动学习中的作用。为了弥补这一差距， 知识，这项建议利用新的行为范式，在小鼠中熟练地伸展，细胞类型特定于 行为过程中的活体记录，以及小脑输出的因果光遗传操作。我会先来 确定如何调整INTA活动以确保不同目标的终点精确度。为此，我将 检查INTA神经动力学，包括大小和时序，以及它们与关键运动学的关系 达到精度的参数。其次，我将测试INTA的预期控制信号是否能够适应 考虑到REACH扰动。跨越电路和行为层面，这项建议旨在理解 小脑输出在协调运动的预期运动控制中的作用。