Neural Basis for Cerebellar Motor Learning

 描述(申请人提供)：小脑是学习运动技能的关键。自60‘年S和70’年S以来，该领域一直在“小脑学习理论”的框架内工作：攀登纤维输入到小脑的信号错误；攀登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抑制；这种“长期抑郁”(LTD)导致在随后的运动中浦肯野细胞的单峰放电发生变化；小脑输出的变化引起运动成绩的逐渐改善，消除运动错误。随后的行为和神经研究表明，学习是由几个大脑部位的多种可塑性机制调节的。目前的方案利用清醒、行为正常的猴子顺畅的追逐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。该提案首先将描述行为学习的多个组成部分的发展过程，特别是需要重复学习刺激以巩固的组成部分。接下来，计划中的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之间的神经联系。 眼球运动；绒毛复合体中的浦肯野细胞，其前庭核中的靶神经元(FTN)，以及与动眼蠕虫中的追踪有关的浦肯野细胞。絮状复合体已经被牵连到学习的单次试验成分中，拟议的研究将询问合并学习是否也在那里出现。来自其他区域的记录将提供关于神经学习在多大程度上局限于小叶复合体的量化结论，以及学习的多个组成部分是否在回路中不同位置的不同时间进程中进化。运动技能学习是让人类在中风后重新学习旧动作，并在神经系统老化时保持出色运动功能的基本机制。对运动学习的神经回路机制的了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.