Neural Basis for Cerebellar Motor Learning

 描述（由申请人提供）：小脑对于运动技能的学习至关重要。自60年代和70年代以来，该领域一直在“小脑学习理论”的框架内工作：小脑的攀爬纤维输入信号在运动中的错误;攀爬纤维输入和平行纤维活动的结合导致从活跃的平行纤维到浦肯野细胞树突的突触的抑制;这种“长期抑制”（LTD）导致浦肯野细胞在随后的运动中的简单尖峰放电的变化;并且小脑输出的变化导致运动表现的逐渐改善并消除运动错误。随后的行为和神经研究表明，学习是由多个大脑部位的多种可塑性机制介导的。目前的提议使用清醒的、行为正常的猴子的平滑的眼球运动来理解完整的神经回路是如何组织运动技能学习的。该建议首先将描述行为学习的多个组成部分的发展的时间过程，特别是需要重复学习刺激来巩固的组成部分。接下来，本实验将研究小脑追踪回路中三个不同区域的不同学习成分的神经相关性 眼球运动;絮状复合体中的浦肯野细胞，前庭核中的靶神经元（FTNs），以及眼蚓部中与追踪相关的浦肯野细胞。絮状复合体已经与学习的单一试验成分有关，拟议中的研究将询问巩固学习是否也存在于其中。来自其他区域的记录将允许关于神经学习在絮状复合体中定位的程度的定量结论，以及学习的多个组成部分是否在回路中的不同部位随着不同的时间过程而演变。运动技能学习是使人类在中风后重新学习旧动作的重要机制，并且随着神经系统老化而保持良好的运动功能。对运动学习的神经回路机制的理解将有助于运动障碍和中风的临床治疗。

 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.