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.

项目概要/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，以预测异常行为 行动，并且在回忆这些关联的过程中，它将施加适应性变化以灌输纠正行为。这 记忆过程取决于可塑性，可塑性通过学习的模式改变小脑的输出 浦肯野细胞峰值输出。分子层中间神经元 (MLI) 受到平行纤维的激发，这些纤维传递 感觉运动信息通过苔藓纤维通路传递，进而对神经元施加前馈抑制 突触后浦肯野细胞减少其尖峰输出。 MLI 突触是塑料的，因此可能是 容易受到学习诱导的修饰的影响，从而改变它们对浦肯野细胞的抑制影响，并且 通过这种方式，赋予适应性行为。然而，对 MLI 如何受经验影响以及是否 他们的活动对于表达学习的必要性是未知的，从而造成了知识差距 了解小脑功能。因此，本研究的目的是阐明 MLI 在 行为小鼠的适应性运动控制，并测量学习诱导的反应特性的可塑性。 这将通过两个目标来实现。首先，我们将使用电生理学和基因编码效应器 在运动学习行为期间测量和操纵体内 MLI 反应的活动：适应 前庭眼反射（VOR）。这将使我们能够确定学习是否会改变 MLI 的激活方式 感觉运动刺激以及它们的抑制输出是否对于浦肯野细胞尖峰模式的变化是必要的 以及习得的眼球运动的表达。在第二个目标中，小脑的定量测量 接受 VOR 学习的小鼠切片制剂将用于确定 MLI 是否表现出活性 - 诱导其突触特性的可塑性。这项研究采用创新的多学科方法 破译允许小脑编码运动记忆的细胞和电路水平机制 学习并实施适应性运动行为。完成这些目标将有助于获得新的见解 了解小脑如何存储和回忆学习记忆。