Motor Memory Storage in the Cerebellum

小脑中的运动记忆存储

• 批准号: 10469662
• 负责人: Jason M Christie
• 金额: $ 41.75万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10469662
• 关键词: Adaptive Behaviors; Address; Affect; Animals; Ataxia; Behavior; Brain; Cell physiology; Cells; Cerebellar Cortex; Cerebellum; Data; Dependence; Dystonia; Electrophysiology (science); Equilibrium; Excitatory Synapse; Exhibits; Eye Movements; Fiber; Fire - disasters; Future; Goals; Impairment; In Vitro; Inferior; Instruction; Interneurons; Knowledge; Lead; Learning; Link; Location; Long-Term Depression; Measurement; Measures; Mediating; Memory; Modeling; Modification; Molecular; Motor; Movement; Movement Disorders; Mus; N-Methyl-D-Aspartate Receptors; Nervous System Physiology; Olives - dietary; Outcome; Output; Pathology; Pathway interactions; Pattern; Persons; Play; Preparation; Process; Property; Purkinje Cells; Quality of life; Role; Signal Transduction; Site; Slice; Stimulus; Structure of purkinje fibers; Synapses; Synaptic plasticity; Testing; Training; Transgenic Mice; Work; awake; deviant; experience; gamma-Aminobutyric Acid; in vivo; innovation; insight; interdisciplinary approach; learned behavior; memory encoding; memory process; memory recall; mossy fiber; motor behavior; motor control; motor disorder; motor learning; neural correlate; novel; optogenetics; postsynaptic; receptor-mediated signaling; response; vestibulo-ocular reflex

Project Summary/Abstract During motor learning, the cerebellum encodes memories of sensorimotor associations that predict deviant action and, during recall of these associations, it will impose adaptive changes to instill corrective behavior. This memory process depends on plasticity that alters the output of the cerebellum through learned patterns of Purkinje cell spike output. Molecular layer interneurons (MLIs) are excited by parallel fibers that convey sensorimotor information relayed through the mossy fiber pathway and, in turn, exert feedforward inhibition onto postsynaptic Purkinje cells to reduce their spike output. MLI synapses are plastic and therefore may be susceptible to learning-induced modification that would alter their inhibitory influence on Purkinje cells and, in this way, impart adaptive behavior. Yet, a basic understanding of how MLIs are affected by experience and if their activity is necessary for the expression of learning is unknown, creating a knowledge gap in the understanding of cerebellar function. Therefore, the objective of this study is to elucidate the role of MLIs in adaptive motor control in behaving mice and measure for learning-induced plasticity in their response properties. This will be accomplished in two aims. In the first, we will use electrophysiology and genetically encoded effectors of activity to measure and manipulate MLI responses in vivo during a motor-learning behavior: adaptation of the vestibulo-ocular reflex (VOR). This will allow us to determine if learning alters how MLIs are activated during sensorimotor stimulation and if their inhibitory output is necessary for pattern changes in Purkinje cell spiking and the expression of learned eye movements. In the second aim, quantitative measurements from cerebellar slice preparations of mice that gave undergone VOR learning will be used to determine if MLIs show activity- induced plasticity in their synaptic properties. This study encompasses an innovative, multidisciplinary approach to decipher the cellular- and circuit-level mechanisms that allow the cerebellum to encode memories of motor learning and implement adaptive motor behavior. Completion of these aims will contribute to novel insights into understanding how the cerebellum stores and recalls memories of learning.

项目总结/摘要 在运动学习过程中，小脑对感觉运动关联的记忆进行编码， 行动，并在回忆这些协会，它将施加适应性的变化，灌输纠正行为。这 记忆过程依赖于可塑性，这种可塑性通过学习的模式来改变小脑的输出。 浦肯野细胞尖峰输出。分子层中间神经元（MLI）由平行纤维激发， 感觉运动信息通过苔藓纤维通路传递，反过来，对 突触后浦肯野细胞，以减少其尖峰输出。MLI突触是可塑性的，因此可能是 易受学习诱导的修饰，这将改变它们对浦肯野细胞的抑制作用， 通过这种方式，赋予适应性行为。然而，对多边机构如何受到经验的影响以及 他们的活动是必要的表达学习是未知的，创造了一个知识差距， 了解小脑的功能。因此，本研究的目的是阐明MLI的作用， 行为小鼠的自适应运动控制和测量其反应特性中的学习诱导的可塑性。 这将通过两个目标来实现。首先，我们将使用电生理学和遗传编码效应器 在运动学习行为期间测量和操纵体内MLI反应的活动： 前庭眼反射（VOR）。这将使我们能够确定学习是否会改变MLI在学习过程中的激活方式。 感觉运动刺激，以及它们的抑制性输出是否是浦肯野细胞峰电位模式变化所必需的 以及学习到的眼球运动的表达。在第二个目标中，定量测量小脑 进行VOR学习的小鼠的切片制备物将用于确定MLI是否显示活性- 诱发了突触特性的可塑性。本研究采用了创新的多学科方法 破译细胞和电路水平的机制，使小脑编码的运动记忆， 学习和实施适应性运动行为。这些目标的实现将有助于对以下问题的新见解： 了解小脑如何储存和回忆学习记忆。