Neural Basis for Cerebellar Motor Learning

小脑运动学习的神经基础

• 批准号: 9101364
• 负责人: STEPHEN G LISBERGER
• 金额: $ 50.42万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2020-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9101364
• 关键词: Age; Architecture; Area; Attenuated; Behavior; Behavioral; Brain; Cerebellar cortex structure; Cerebellar vermis structure; Cerebellum; Child; Clinical; Complex; Data Analyses; Dendrites; Development; Experimental Designs; Eye Movements; Fiber; Generations; Goals; Health; Human; Learning; Link; Long-Term Depression; Measures; Mediating; Mental Depression; Monkeys; Motor; Motor Skills; Movement; Nervous system structure; Neurons; Output; Performance; Phase; Process; Purkinje Cells; Reporting; Research; Shock; Signal Transduction; Site; Smooth Pursuit; Stimulus; Stroke; Structure; Synapses; System; Testing; Time; Vestibular nucleus structure; Work; aging brain; awake; base; course development; forgetting; improved; innovation; learned behavior; motor disorder; motor learning; motor skill learning; neural circuit; neural correlate; neurotransmission; oculomotor; operation; prevent; public health relevance; relating to nervous system; research study; response; skills; theories

 DESCRIPTION (provided by applicant): The cerebellum is critical for learning of motor skills. Since the 60's and 70's, the field has been working within the framework of the "cerebellar learning theory": climbing fiber inputs to the cerebellum signal errors in movements; the conjunction of climbing fiber inputs and parallel fiber activity leads to depression of the synapse from active parallel fibers onto Purkinje cell dendrites; this "long-term depression" (LTD) causes changes in the simple-spike firing of Purkinje cells on subsequent movements; and the change in cerebellar output causes gradual improvements in motor performance and eliminates motor errors. Subsequent behavioral and neural studies suggest that learning is mediated by multiple plasticity mechanisms at several brain sites. The present proposal uses the smooth pursuit eye movements of awake, behaving monkeys to understand how a full neural circuit single organizes motor skill learning. The proposal first will describe the time course of development of multiple components of behavioral learning, especially a component that requires repetition of learning stimuli to consolidate. Next, the proposed experiments will study neural correlates of the different components of learning in three different areas in the cerebellar circuit for pursuit eye movements; Purkinje cells in the floccular complex, their target neurons (FTNs) in the vestibular nucleus, and Purkinje cells related to pursuit in the oculomotor vermis. The floccular complex already has been implicated in a single-trial component of learning, and the proposed research will ask whether consolidated learning also is represented there. Recordings from the other areas will allow quantitative conclusions about the extent to which neural learning is localized in the floccular complex, and whether multiple components of learning evolve over different time courses at different sites in the circuit. Motor skill learning is an essential mechanism for allowing humans to relearn old movements after strokes, and for maintaining excellent motor function as the nervous system ages. An understanding of the neural circuit mechanisms of motor learning should facilitate clinical approaches in motor disorders and stroke.

 描述（由申请人提供）：小脑对于运动技能的学习至关重要，自 20 世纪 60 年代和 70 年代以来，该领域一直在“小脑学习理论”的框架内进行研究：攀爬纤维向小脑输入运动中的错误信号；攀爬纤维输入和平行纤维活动的结合导致突触从活动平行纤维下降到浦肯野细胞树突上，这种“长期抑制”； (LTD) 导致浦肯野细胞运动时的简单尖峰放电发生变化；小脑输出的变化导致运动性能逐渐改善，并消除运动错误，随后的行为和神经研究表明，学习是由多种可塑性机制介导的。本提案利用清醒、有行为能力的猴子的平滑追踪眼球运动来理解完整的神经回路如何组织运动技能学习。这需要重复接下来，拟议的实验将研究小脑回路中三个不同区域的学习不同组成部分的神经相关性。 眼球运动；絮状复合体中的浦肯野细胞、前庭核中的目标神经元（FTN）以及与动眼神经蚓部中的追踪相关的浦肯野细胞已经与学习的单次试验成分有关。拟议的研究将询问来自其他领域的整合学习记录是否也代表了神经学习在絮状复合体中的定位程度，以及学习的多个组成部分是否进化。运动技能学习是人类在中风后重新学习旧运动以及随着神经系统老化而保持良好运动功能的重要机制。应促进运动障碍和中风的临床方法。