Cortical Control of Hindlimb Muscles in Primates

描述(由申请人提供)：正常和功能障碍的皮质运动控制的机制是一个具有重要神经生物学和临床重要性的课题。皮质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直接相关。虽然多年来，灵长类动物对手臂和手的皮质控制一直是相当关注的焦点，也是大量研究的主题，但对于包括人类在内的灵长类动物来说，对下肢的皮质控制相对较少，尽管它在临床和运动技能中都具有明显的重要性。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和初级运动皮质(M1)之间的突触联系的一些基本特征，包括存在单突触联系，这表明一种类似于手臂和手运动神经元的突触联系。虽然突触学方面的工作有些有限，但它仍然为清醒的灵长类动物的额外功能研究奠定了必要的基础。这项建议的总体目标是回答有关后肢皮质控制的功能特性和组织的基本问题，朝着开发与前肢平行的知识库的更大目标。为此，我们提出了以下六个具体目标：1)确定后肢M1皮质与前肢皮质输出的肌肉协同作用的特性；2)确定后肢M1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皮质与前肢M1皮质运动神经元的突触联系的强度和性质；4)表征后肢M1皮质触发平均刺激(StTA)中突出的晚期促进峰(S)的特性，并确定这些晚期峰背后的神经机制5)比较同侧后肢肌肉的M1输出效应与对侧肌肉的输出效应的特点；6)利用棘波和刺激触发的肌电活动平均值，确定猴M1皮层对快、慢伸踝肌的输出效应的性质。与公共卫生相关的大脑皮质和皮质脊髓神经元损伤与中风、肌萎缩侧索硬化症、创伤性脑损伤和脊髓损伤相关，会导致严重的下肢损伤，导致相当大的残疾和患者生活质量的下降。这项建议侧重于描绘正常的皮质输出组织到下肢肌肉的特征。这项工作得出的数据将适用于理解与大脑皮层损伤相关的后肢运动障碍，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.