Motor cortical control of voluntary forelimb muscle activity

运动皮质控制自愿前肢肌肉活动

• 批准号: 9560617
• 负责人: Claire Louise Warriner
• 金额: $ 4.4万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9560617
• 关键词: Action Potentials; Acute; Animals; Axon; Behavior; Behavior Control; Behavioral Paradigm; Cells; Chronic; Contracts; Cues; Data; Electrodes; Ensure; Equilibrium; Extensor; Felis catus; Flexor; Forelimb; Generations; Goals; Human; Implant; Individual; Injection of therapeutic agent; Interneurons; Joints; Label; Limb structure; Locomotion; Mediating; Monkeys; Motor; Motor Cortex; Motor Neurons; Movement; Mus; Muscle; Neurons; Optics; Periodicity; Phase; Play; Population; Proteins; Recruitment Activity; Reporting; Research; Role; Running; Sensory; Silicon; Spinal; Spinal Cord; Spinal cord injury patients; Subgroup; Synapses; System; Techniques; Testing; Time; Training; Triceps Brachii Muscle; Viral Vector; Visual; Volition; Width; base; behavioral outcome; biceps brachii muscle; cell type; experimental study; extracellular; limb movement; mind control; motor impairment; neural circuit; neural prosthesis; neurodevelopment; neuromechanism; neuroregulation; novel; optogenetics; relating to nervous system; selective expression; sensory feedback; stroke treatment

Project summary/abstract The alternating contraction of opposing flexor and extensor muscles, known as antagonist pairs, creates the rhythmic limb movement of locomotion. This phenomenon is regulated in part by reciprocal inhibition: sensory feedback from an active muscle excites the Ia interneuron, which then inhibits that muscle's antagonist. However, when a task requires limb stiffness and joint stability, this circuit must be overridden to allow co-contraction of both flexor and extensor muscles. Previous studies have indicated that motor cortex is responsible for the reduction of reciprocal inhibition observed during voluntary co-contraction, but its mechanism of action is unknown. Elucidating how motor cortex recruits spinal circuits to permit antagonist muscle co-contraction will further our understanding of the neural control of voluntary movement. Monkey and cat studies have reported that intracortical inhibition is reduced during voluntary co- contraction, indicating that this reduction may be necessary for co-contraction. Neural recording studies in monkey found that a discrete population of corticospinal neurons (CSNs) increases its activity during co- contraction but not during extension or flexion, indicating that increased CSN activity may be required for this behavior. Of the CSNs, a subgroup that synapses on a type of spinal interneuron known as the GABApre (CSN-GABApres) is a likely candidate for antagonist muscle control. This is supported by findings that indicate the GABApre interneuron is capable of reducing reciprocal inhibition and that the type of inhibition GABApres exert is increased during co-contraction. This evidence leads us to hypothesize that during this behavior, intracortical inhibition is decreased, the activity of CSNs, in particular CSN-GABApres, is increased, and that this activity is necessary for voluntary co-contraction. To test these hypotheses, we will record motor cortical activity in mouse during a novel behavioral paradigm that elicits either co-contraction or alternation of the forelimb triceps-biceps antagonist muscle pair. Putative cortical interneurons will be identified by the width of their action potential waveform and CSNs will be identified by optogenetic activation of their axons. A novel tracing technique will also allow the optical identification of CSN-GABApres during recording. The importance of CSN and CSN-GABApre activity to the reduction of spinal reciprocal inhibition and thus the execution of co-contraction will be tested by optogenetic inactivation of these cells during co-contraction as compared to alternation. The findings generated by these experiments will clarify the neural mechanisms that underlie the control of antagonist muscles and voluntary movement. This information could eventually be applied to treatment for stroke and spinal cord injury patients or contribute to the development of neural prostheses for movement-impaired individuals.

项目概要/摘要 相对的屈肌和伸肌的交替收缩，称为拮抗肌对， 创造有节奏的肢体运动。这种现象部分受到相互调节 抑制：来自活跃肌肉的感觉反馈会兴奋 Ia 中间神经元，然后抑制该肌肉的 对手。然而，当任务需要肢体僵硬和关节稳定性时，必须重写该电路以 允许屈肌和伸肌共同收缩。先前的研究表明运动皮层 负责减少自愿共同收缩期间观察到的相互抑制，但其 作用机制未知。阐明运动皮层如何招募脊髓回路以允许拮抗剂 肌肉共同收缩将进一步加深我们对随意运动的神经控制的理解。 猴子和猫的研究报告说，在自愿共同参与的过程中，皮质内抑制会减少。 收缩，表明这种减少可能是共同收缩所必需的。神经记录研究 猴子发现，皮质脊髓神经元（CSN）的离散群体在共同作用期间增加了其活性 收缩但不在伸展或屈曲期间，表明可能需要增加 CSN 活动 行为。在 CSN 中，一个与称为 GABApre 的脊髓中间神经元突触的亚组 (CSN-GABApres) 可能是拮抗肌控制的候选者。调查结果表明，这一点得到了支持 GABApre 中间神经元能够减少相互抑制，并且抑制类型 GABApres 共同收缩期间用力增加。这一证据使我们推测，在这种行为过程中， 皮质内抑制减少，CSN（特别是 CSN-GABApres）的活性增加，并且 这项活动对于自愿收缩是必要的。 为了测试这些假设，我们将记录小鼠在新的行为过程中的运动皮层活动 引起前肢三头肌-二头肌拮抗肌对的共同收缩或交替的范例。 假定的皮质中间神经元将通过其动作电位波形的宽度来识别，并且 CSN 将被 通过轴突的光遗传学激活来识别。一种新颖的追踪技术也将允许光学 记录过程中 CSN-GABApres 的识别。 CSN 和 CSN-GABApre 活性对 脊髓相互抑制的减少以及共同收缩的执行将通过光遗传学进行测试 与交替相比，这些细胞在共收缩期间失活。这些结果产生 实验将阐明控制拮抗肌和随意肌的神经机制 移动。这些信息最终可以应用于中风和脊髓损伤患者的治疗 或为运动障碍人士开发神经假体做出贡献。