Motor Memory Storage in the Cerebellum

项目摘要/摘要 在运动学习过程中，小脑对预测异常的感觉运动联想的记忆进行编码 行动，在回忆这些关联的过程中，它将强制实施适应性变化，以灌输纠正行为。这 记忆过程依赖于可塑性，它通过学习的模式改变小脑的输出 浦肯野细胞棘波输出。分子层中间神经元(MLI)由平行的纤维兴奋，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 突触后浦肯野细胞，以减少它们的尖峰输出。MLI突触是塑料的，因此可能是 容易受到学习诱导的修饰，这将改变它们对浦肯野细胞的抑制影响，在 这样，就可以赋予适应性行为。然而，对MLI如何受到经验的影响以及是否 他们的活动对于表达未知的学习是必要的，造成了知识上的鸿沟 对小脑功能的了解。因此，本研究的目的是阐明MLI在以下方面的作用 行为小鼠的适应性运动控制及其反应特性中学习诱导可塑性的测量。 这将通过两个目标实现。首先，我们将使用电生理学和基因编码的效应器 在运动学习行为中测量和操纵体内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在 感觉运动刺激及其抑制输出是否是浦肯野细胞棘波模式改变所必需的 以及习得眼球运动的表情。在第二个目标中，从小脑进行定量测量 给予VOR学习的小鼠的切片制剂将用于确定MLI是否显示出活性- 诱导突触特性的可塑性。这项研究包含了一种创新的、多学科的方法 破译允许小脑对运动记忆进行编码的细胞和电路级别的机制 学习和实施适应性运动行为。完成这些目标将有助于对 了解小脑是如何存储和回忆学习记忆的。

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.