Neural circuits underlying the acquisition and control of motor skills

运动技能获取和控制的神经回路

• 批准号: 9218242
• 负责人: Bence P Olveczky
• 金额: $ 36.97万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9218242
• 关键词: Accelerometer; Address; Affect; Animals; Basal Ganglia; Behavior; Behavior monitoring; Behavioral; Bilateral; Biological Models; Brain Stem; Cell Nucleus; Chronic; Collection; Complex; Corpus striatum structure; Data; Data Set; Globus Pallidus; Goals; Learning; Learning Skill; Lesion; Link; Logic; Midbrain structure; Molecular; Motor; Motor Cortex; Motor Skills; Motor output; Movement; Neurons; Neurorehabilitation; Neurosciences; Output; Pathway interactions; Patients; Population; Process; Rattus; Research; Resolution; Rodent; Role; Stereotyping; Stroke; Structure; System; Techniques; Testing; Thalamic structure; Training; Viral; Work; Writing; arm; clinical practice; clinically significant; cohort; design; disability; kinematics; motor learning; motor skill learning; nervous system disorder; neural circuit; neuromechanism; novel therapeutics; relating to nervous system; skills; skills training; tutoring

Neural circuits underlying the acquisition and control of motor skills Much of our behavioral repertoire consists of learned motor skills, yet little is known about the neural mechanisms that underlie their acquisition and execution. We have recently discovered that motor cortex is required for learning but not for executing certain motor skills, suggesting an autonomous subcortical motor network capable of generating task-specific learned motor sequences. Importantly, motor cortex seems to be involved in ‘tutoring’ this subcortical network during learning. Here we will first explore the role of the basal ganglia, a collection of motor-related midbrain nuclei of great clinical significance, in the storage and execution of complex task-specific motor sequences. Specifically, we will test whether the part of the basal ganglia that receives input from motor cortex, the dorsolateral striatum (DLS), is essentially involved in producing the skills we train. We will do this by way of lesioning DLS and other parts of the basal ganglia in animals that have learned to master the task we train (Aim 1). We will further analyze how the striatum encodes the learned motor sequences, specifically testing the hypothesis that it encodes the detailed structure and kinematics of learned motor sequences (Aim 2). Lastly, we will test the idea that motor cortex is ‘tutoring’ the subcortical motor circuits during learning through its projections to the basal ganglia (Aim 3). We will explore these questions using a fully automated rodent training system we developed, in combination with a set-up for recording neural activity and behavior continuously over weeks and months in freely behaving rodents. Addressing the aims of our proposal will clarify the logic of how the mammalian motor system acquires and controls task-specific motor sequences, and delineate the roles of the BG and the corticostriatal pathway in these important processes, thus addressing fundamental questions in neuroscience with far-reaching implications for clinical practice and neurorehabilitation.

运动技能获得和控制的神经回路 我们的大部分行为都是由习得的运动技能组成的，但对神经系统的了解却很少。 这些机制是其获取和执行的基础。我们最近发现运动皮层 需要学习，但不是执行某些运动技能，这表明自主的皮层下运动 网络能够生成任务特定的学习运动序列。重要的是，运动皮层似乎 在学习过程中参与“辅导”这个皮层下网络。 在这里，我们将首先探讨基底神经节的作用，基底神经节是运动相关的中脑核团的集合， 在存储和执行复杂的特定任务运动序列方面具有重要的临床意义。具体地说， 我们将测试是否基底神经节的一部分，接受来自运动皮层的输入，背外侧 纹状体（DLS）基本上参与产生我们训练的技能。我们将通过损伤DLS来实现这一点 和其他部位的基底神经节，这些动物已经学会了掌握我们训练的任务（目标1）。我们将 进一步分析纹状体如何编码学习的运动序列，特别是测试假设， 它对学习的运动序列的详细结构和运动学进行编码（Aim 2）。最后，我们将测试 这种观点认为，在学习过程中，运动皮层通过投射到大脑皮层， 基底神经节（Aim 3）。我们将使用一个全自动的啮齿动物训练系统来探索这些问题， 开发了一种装置，用于连续数周记录神经活动和行为 在自由活动的啮齿类动物中存活了数月。 解决我们的建议的目的将澄清哺乳动物运动系统如何获得的逻辑 并控制任务特定的运动序列，并描绘BG和皮质纹状体通路在 这些重要的过程，从而解决神经科学中的基本问题， 对临床实践和神经康复的影响。