Motor cortical control of voluntary forelimb muscle activity

项目概要/摘要 相反的屈肌和伸肌的交替收缩，被称为拮抗肌对， 创造了有节奏的肢体运动。这一现象部分是由互惠调节的 抑制：来自活动肌肉的感觉反馈兴奋Ia中间神经元，然后抑制该肌肉的 拮抗剂然而，当任务需要肢体僵硬和关节稳定性时，必须覆盖该电路， 允许屈肌和伸肌共同收缩。以前的研究表明，运动皮层是 负责减少相互抑制观察自愿共同收缩，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，皮质内抑制减少自愿合作， 收缩，表明这种减少可能是必要的共同收缩。神经记录研究 猴子发现，一个离散的群体皮质脊髓神经元（CSNs）增加其活动，在共同- 收缩，但不是在伸展或屈曲，表明增加CSN活动可能需要这一点 行为在CSN中，一个亚群与一种称为GABApre的脊髓中间神经元突触 （CSN-GABApres）是拮抗剂肌肉控制的可能候选者。研究结果表明， GABApre中间神经元能够减少相互抑制，并且抑制GABApre的类型 在共同收缩期间，施加增加。这一证据使我们假设，在这种行为中， 皮质内抑制降低，CSN，特别是CSN-GABApres的活性增加， 这种活动是自愿共同收缩所必需的。 为了验证这些假设，我们将在一个新的行为过程中记录小鼠的运动皮层活动， 范例，其激发前肢三头肌-二头肌拮抗肌对的共同收缩或交替。 将通过其动作电位波形的宽度来识别推定的皮层中间神经元，并且将通过其动作电位波形的宽度来识别CSN。 通过轴突的光遗传学激活来识别。一种新的跟踪技术也将允许光学 在记录期间鉴定CSN-GABApres。CSN和CSN-GABApre活性对 脊髓相互抑制的减少以及因此共收缩的执行将通过光遗传学方法测试。 与交替相比，这些细胞在共同收缩期间失活。这些调查结果 实验将阐明控制拮抗肌和自主神经的神经机制。 运动这一信息最终可以应用于中风和脊髓损伤患者的治疗 或有助于为运动障碍个体开发神经假体。

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.