Motor Skill and the Cortical Motor Areas

运动技能和皮质运动区域

• 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
• 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

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.

项目总结 熟练的连续动作的获得和保持是人类行为的基本部分。 我们仍然对大脑皮质运动区何时何地发生可塑性变化知之甚少。 保持熟练的顺序动作。在这里，我们建议研究学习和学习的时间演变 维持初级运动皮质(M1)和背侧运动前皮质(PMD)的熟练顺序运动 通过对这些区域的信息存储进行药理学操作。 我们将训练猴子执行两项任务。在一项任务中，猴子进行顺序伸展 由记忆引导的动作。记忆引导的顺序动作任务的技能是通过 相当多的练习。对于控制任务，猴子在视觉提示的引导下执行伸展运动。 我们的初步数据显示，注射蛋白质合成抑制剂或DNA抑制剂 猴子M1基因的甲基化扰乱了获得性顺序动作的表现，而不影响 视觉导引触觉的表现。我们将应用这些方法来检查性质和时间 M1和PMD的可塑性过程过程支持广泛的学习和维持 练习运动技能。首先，确定连续运动的神经轨迹是否逐渐 在M1中巩固与扩展实践，我们将注入一种蛋白质合成的抑制剂到M1的多倍 学习顺序动作的时间点。我们假设运动技能是重复的 每次通过蛋白质合成来巩固一门学科的练习，而且巩固的速度下降 随着学习的进行。第二，确定PMD何时参与学习之间的关联 序列中的运动元素，我们将多次向PMD注入蛋白质合成的抑制剂 学习顺序动作时的点数。我们假设M1和PMD中的学习过程 在不同的时间范围内运作。第三，确定M1和PMD是否成为长期储存的地点 对于所获取的顺序运动，并且保持对所获取的顺序运动的维护至关重要 运动时，我们将向这些区域注射一种DNA甲基化抑制剂。我们假设注资将会 在长期练习后干扰记忆引导的顺序动作的维持，并且 猴子需要重新学习注射后的序列，以恢复他的表现。 建议的研究完成后，将会加深我们对地球的时间演变的了解。 学习，随着动物通过不断的长期练习和巩固慢慢变得高度熟练。那个级别 运动序列的专门知识从来没有在啮齿类动物身上研究过，也很少在猴子身上研究过，但这是 每天的人体运动表现。研究结果将为制定新的战略提供信息。 获得运动技能，促进中风或创伤性脑损伤后的功能恢复。