Motor Skill and the Cortical Motor Areas

运动技能和皮质运动区域

基本信息

批准号：
10559036
负责人：
Machiko Obayashi (Ohbayashi)
金额：
$ 39.75万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-12-15 至 2027-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10559036
关键词：
Affect Animals Area Behavior Cues DNA Methylation Data Decitabine Dorsal Elements Evolution Functional Magnetic Resonance Imaging Funding Gene Expression Gene Expression Regulation Human Information Storage Injections Learning Learning Skill Lesion Maintenance Memory Metabolic Monkeys Motor Motor Cortex Motor Neurons Motor Skills Movement Nature Neurons Performance Phase Process Protein Biosynthesis Protein Synthesis Inhibition Protein Synthesis Inhibitors Recovery of Function Rodent Signal Transduction Site Stroke Synaptic plasticity Testing Time Training Traumatic Brain Injury Visual design experimental study frontal lobe gray matter inhibitor memory consolidation neural nonhuman primate pharmacologic sequence learning skills visual performance

Affect Animals Area Behavior Cues DNA Methylation Data Decitabine Dorsal Elements Evolution Functional Magnetic Resonance Imaging Funding Gene Expression Gene Expression Regulation Human Information Storage Injections Learning Learning Skill Lesion Maintenance Memory Metabolic Monkeys Motor Motor Cortex Motor Neurons Motor Skills Movement Nature Neurons Performance Phase Process Protein Biosynthesis Protein Synthesis Inhibition Protein Synthesis Inhibitors Recovery of Function Rodent Signal Transduction Site Stroke Synaptic plasticity Testing Time Training Traumatic Brain Injury Visual design experimental study frontal lobe gray matter inhibitor memory consolidation neural nonhuman primate pharmacologic sequence learning skills visual performance

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项目摘要

PROJECT SUMMARY The acquisition and retention of skilled sequential movements is a fundamental part of human behavior. We still know little about where and when plastic changes occur in the cortical motor areas to learn and maintain skilled sequential movements. Here, we propose to study the temporal evolution of the learning and maintenance of skilled sequential movements in primary motor cortex (M1) and dorsal premotor cortex (PMd) by pharmacologically manipulating information storage in these areas. We will train monkeys to perform two tasks. In one task, the monkeys perform sequential reaching movements guided by memory. Skill on the memory-guided sequential movements task is acquired through considerable practice. For a control task, the monkeys perform reaching movements guided by visual cues. Our preliminary data showed that an injection of an inhibitor for protein synthesis or an inhibitor for DNA methylation into M1 of monkeys disrupted the performance of acquired sequential movements without affecting the performance of visually guided reaching. We will apply these approaches to examine the nature and time course of plasticity processes in M1 and PMd that support the learning and maintenance of extensively practiced motor skills. First, to determine whether the neural trace for sequential movements is gradually consolidated in M1 with extended practice, we will inject an inhibitor of protein synthesis into M1 at multiple time points during learning of sequential movements. We hypothesize that the motor skill is repetitively consolidated through protein synthesis every time a subject practice, and that the rate of consolidation declines as learning proceeds. Second, to determine when PMd is involved in learning the associations between movement elements in a sequence, we will inject an inhibitor of protein synthesis into PMd at multiple time points during learning of sequential movements. We hypothesize that learning processes in M1 and PMd operate in different time frames. Third, to determine whether M1 and PMd become sites of long-term storage for the acquired sequential movements and remain critical for the maintenance of the acquired sequential movements, we will inject an inhibitor of DNA methylation into these areas. We postulate that the injection will disrupt the maintenance of memory-guided sequential movements after long term practice and that the monkey will need to relearn the sequence to recover his performance after the injection. Completion of the proposed studies will expand our understanding of the temporal evolution of the learning, as animals slowly become highly skilled with ongoing long-term practice and consolidation. That level of motor sequence expertise is never studied in rodents and rarely in monkeys, yet it is a common feature of everyday human motor performance. The results will provide information to develop new strategies for acquiring motor skills and enhance functional recovery following stroke or traumatic brain injury.

项目摘要熟练的顺序运动的获取和保留是人类行为的基本组成部分。我们仍然对皮质运动区域中的塑料发生变化的何时何时了解和保持熟练的顺序运动。在这里，我们建议研究学习的时间演变和维持一级运动皮层（M1）和背前皮层（PMD）中熟练的顺序运动通过药理操纵这些区域的信息存储。我们将训练猴子执行两项任务。在一项任务中，猴子执行顺序到达动作由内存引导。通过记忆引导的顺序运动任务是通过实践很大。对于控制任务，猴子执行以视觉提示为指导的运动。我们的初步数据表明，注射蛋白质合成抑制剂或DNA抑制剂在猴子的M1中甲基化破坏了获得的顺序运动的性能而不会影响视觉引导到达的性能。我们将采用这些方法来检查性质和时间 M1和PMD中的可塑性过程，支持广泛学习和维护练习运动技能。首先，确定顺序运动的神经跟踪是否逐渐通过扩展实践合并在M1中，我们将在多个处注入蛋白质合成的抑制剂学习顺序运动期间的时间点。我们假设运动技能是重复的每当主题实践时，通过蛋白质合成巩固，合并速率下降随着学习的进行。第二，确定何时涉及PMD参与学习之间的关联序列运动元素，我们将多次将蛋白质合成的抑制剂注入PMD中在学习顺序运动的过程中。我们假设M1和PMD中的学习过程在不同的时间范围内运行。第三，确定M1和PMD是否成为长期存储的站点对于获得的顺序运动，对于维持获得的顺序至关重要运动，我们将向这些区域注入DNA甲基化的抑制剂。我们假设注射将长期练习后，破坏记忆引导的顺序运动的维护，猴子将需要重新学习序列，以恢复注射后的表现。拟议研究的完成将扩大我们对学习，随着动物逐渐熟练地擅长长期实践和巩固。那个级别运动序列专业知识从未在啮齿动物中研究，很少在猴子中研究，但这是一个共同的特征日常的人类运动性能。结果将提供信息，以制定新的策略获得运动技能并增强脑部或创伤性脑损伤后的功能恢复。