Cortical Control of Hindlimb Muscles in Primates

描述（由申请人提供）：正常和功能失调的皮层运动控制机制是一个具有重要神经生物学和临床意义的话题。皮层组织的特征已被证明与正常运动以及中风和脑瘫等情况下的运动障碍方面直接相关。多年来，灵长类动物的手臂和手的皮质控制一直是人们关注的焦点，也是大量研究的主题，尽管下肢的皮质控制在临床上和包括人类在内的灵长类动物的运动中都很重要，但人们对下肢的皮质控制知之甚少。在麻醉猕猴和狒狒的早期工作中，已经建立了后肢运动神经元与初级运动皮层（M1）之间突触连接的一些基本特征，包括单突触连接的存在，表明其突触连接类似于手臂和手部运动神经元。虽然突触学的研究在一定程度上受到限制，但它仍然为清醒灵长类动物的其他功能研究奠定了必要的基础。本提案的总体目标是回答关于后肢皮质控制的功能特性和组织的基本问题，以实现开发与前肢相似的知识库的更大目标。为此，我们提出以下六个具体目标：1)确定后肢M1皮层输出与前肢皮层输出所代表的肌肉协同作用的性质；2)确定M1后肢肌肉表征与前肢肌肉表征的基本特征；3)确定灵长类动物后肢M1皮层与20个后肢肌肉运动神经元突触连接的强度和性质，并与前肢M1皮层进行比较。4)表征M1皮层刺激触发平均（stta）中显著的后期促进峰的特性，并确定这些后期峰背后的神经机制；5)确定M1输出对同侧后肢肌肉的影响特征，并与对侧肌肉的影响进行比较；6)利用脉冲和刺激触发的肌电图平均来确定猴M1皮层到快、慢踝关节伸肌的输出效应的性质。与中风、肌萎缩侧索硬化症、创伤性脑损伤和脊髓损伤相关的大脑皮层和皮质脊髓神经元损伤会对下肢造成严重损伤，导致相当程度的残疾，并降低患者的生活质量。这一建议的重点是描绘正常皮层输出组织到下肢肌肉的特征。从这项工作中获得的数据将适用于理解与大脑皮层损伤相关的后肢运动缺陷，并可能为治疗干预提供新的策略。

DESCRIPTION (provided by applicant): The mechanisms underlying normal and dysfunctional cortical control of movement is a topic of great neurobiological and clinical importance. Features of cortical organization have been shown to relate directly to normal movement as well as aspects of movement disorders in conditions such as stroke and cerebral palsy. While the cortical control of the arm and hand in primates has been the focus of considerable attention over many years and the subject of a large number of studies, comparatively little is known about the cortical control of the lower extremity despite its obvious importance both clinically and in the motor repertoire of primates including humans. Early work in anesthetized macaques and baboons has established some basic features of the synaptic linkage between hindlimb motoneurons and primary motor cortex (M1), including the existence of monosynaptic connections, suggesting a synaptic linkage similar to that for arm and hand motoneurons. While the work on synaptology has been somewhat limited, it nevertheless forms an essential foundation for additional functional studies in awake primates. The overall objective of this proposal is to answer fundamental questions about the functional properties and organization of hindlimb cortical control toward a larger goal of developing a knowledge base that parallels that for the forelimb. Toward this goal, we propose the following six specific aims: 1) to determine the properties of muscles synergies represented in the output of hindlimb M1 cortex, in comparison to forelimb cortex, 2) to identify basic features of M1 hindlimb muscle representation in comparison with the forelimb muscle representation, 3) to determine the strength and nature of the synaptic linkage from hindlimb M1 cortex in the primate to motoneurons of 20 hindlimb muscles in comparison to that from forelimb M1 cortex, 4) to characterize the properties of the prominent late facilitation peak(s) in stimulus triggered averages (StTAs) of hindlimb muscles from M1 cortex and to determine the neural mechanism underlying these late peaks, 5) to determine the characteristics of M1 output effects on ipsilateral hindlimb muscles in comparison to effects on contralateral muscles, and 6) to determine the nature of output effects from M1 cortex to fast and slow ankle extensor muscles in the monkey using spike and stimulus triggered averaging of EMG activity. PUBLIC HEALTH RELEVANCE Damage to the cerebral cortex and corticospinal neurons associated with stroke, ALS, traumatic brain injury and spinal cord injury produce severe impairments of the lower extremity that lead to considerable disability and reduction in the patient's quality of life. This proposal focuses on delineating features of normal cortical output organization to lower extremity muscles. The data derived form this work will be applicable to understanding hindlimb motor deficits associated with damage to the cerebral cortex and may suggest new strategies for therapeutic intervention.