Cortical Control of Motor Learning

运动学习的皮质控制

• 批准号: 10349469
• 负责人: Takaki Komiyama
• 金额: $ 38.69万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10349469
• 关键词: Address; Affect; Aging; Alzheimer' s Disease; Animals; Area; Attention deficit hyperactivity disorder; Behavior; Behavioral; Brain; Data; Dementia; Dendritic Spines; Diagnosis; Diagnostic; Disease; Environment; Excitatory Synapse; Exhibits; Forelimb; Functional Imaging; Goals; Head; Human; Image; Joystick; Knowledge; Lead; Learning; Learning Disorders; Maps; Mediating; Memory; Modification; Motor; Motor Cortex; Movement; Mus; Neurons; Parkinson Disease; Pattern; Performance; Personal Satisfaction; Phase; Population; Process; Publications; Research; Resolution; Series; Specificity; Stroke; Synapses; Synaptic plasticity; Technology; Testing; Time; Training; Vertebral column; age related; base; excitatory neuron; experience; experimental study; frontier; imaging properties; improved; in vivo two-photon imaging; innovation; motor behavior; motor control; motor disorder; motor learning; neural circuit; novel; optogenetics; postsynaptic neurons; programs; rehabilitation strategy; relating to nervous system; sample fixation; serial imaging; tool; two-photon

Project Summary The ability to learn from experience is one of the most fundamental features of neural circuits. Changes in synaptic connections in specific circuits underlie experience-dependent circuit modifications essential for learning. A detailed understanding of this process is important, not just to understand the mechanisms of learning, but also to better diagnose and treat conditions that affect memory abilities, such as Alzheimer's disease, aging-related dementia, and Parkinson's disease. Our ultimate goal is to understand the precise, fine- scale circuit modifications that support learning. One of the fundamental forms of learning is motor learning in which animals adjust the way they move their bodies to fit their behavioral goals. Among a number of brain areas involved in motor learning, the primary motor cortex (M1) is a major locus where changes take place during motor learning. Many types of changes in M1 have been described that accompany motor learning, including changes of the somatotopic map, neural population activity changes, and synaptic plasticity. However, it is unclear whether M1 is always involved in the control of movements throughout learning and overtraining. Furthermore, the precise functional reorganization of synaptic inputs in M1 during motor learning is only beginning to be understood. We will address these two questions using cutting-edge technologies in mice. Mice under head-fixation will be trained in a forelimb-based motor learning task daily over weeks. In Aim 1, we will perform longitudinal recording of M1 neural populations during months of motor learning and overtraining. Combined with optogenetic perturbation of M1 activity at various phases of training, we test the hypothesis that a movement that is dependent on M1 early in learning can become M1-independent with long-term overtraining. This will also define the period during which the particular motor task we use in the proposal depends critically on M1. Focusing on this period when M1 is critical for motor performance, we will study precise functional reorganization of synapses in M1. We will do this using longitudinal functional imaging at synaptic resolution. In particular, we will test the hypothesis that motor learning induces functional clustering of synaptic inputs related to the learned movements. Such functional clustering would allow the learning-related information to robustly drive circuit activation. These experiments will contribute fundamental neural circuit mechanisms underlying motor learning. Such knowledge could ultimately contribute to a better diagnosis and treatment of motor disorders such as Parkinson's disease and stroke.

项目概要 从经验中学习的能力是神经回路最基本的特征之一。变化 特定电路中的突触连接是依赖于经验的电路修改的基础，这对于 学习。详细了解这个过程很重要，而不仅仅是了解其机制 学习，还可以更好地诊断和治疗影响记忆能力的疾病，例如阿尔茨海默病 疾病、与衰老相关的痴呆症和帕金森病。我们的最终目标是了解精确、精细的 支持学习的规模电路修改。 学习的基本形式之一是运动学习，动物调整它们的移动方式 他们的身体以适应他们的行为目标。在涉及运动学习的许多大脑区域中，主要的 运动皮层 (M1) 是运动学习过程中发生变化的主要部位。多种类型的变化 M1 被描述为伴随运动学习，包括体位图、神经元的变化 群体活动变化和突触可塑性。然而，尚不清楚M1是否总是参与其中 在学习和过度训练过程中控制运动。此外，精准的职能重组 运动学习过程中 M1 突触输入的影响才刚刚开始被理解。我们将解决这两个问题 在小鼠身上使用尖端技术提出问题。头部固定的小鼠将接受基于前肢的训练 几周内每天进行运动学习任务。在目标 1 中，我们将对 M1 神经群体进行纵向记录 在几个月的运动学习和过度训练期间。结合 M1 活性的光遗传学扰动 在训练的各个阶段，我们测试以下假设：在学习早期依赖于 M1 的动作 长期过度训练可能会变得不依赖 M1。这也将定义该期间 我们在提案中使用的特定运动任务主要取决于 M1。关注M1的这段时期 对于运动性能至关重要，我们将研究 M1 突触的精确功能重组。我们会做 这使用突触分辨率的纵向功能成像。特别是，我们将检验以下假设： 运动学习诱导与所学运动相关的突触输入的功能聚类。这样的 功能聚类将允许学习相关信息强有力地驱动电路激活。这些 实验将贡献运动学习的基本神经回路机制。这样的知识 最终可能有助于更好地诊断和治疗帕金森病等运动障碍 和中风。