Cortical Control of Hindlimb Muscles in Primates

灵长类动物后肢肌肉的皮质控制

• 批准号: 8034310
• 负责人: PAUL DAVID CHENEY
• 金额: $ 37.5万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8034310
• 关键词: Anesthetics; Animals; Ankle; Area; Attention; Axon; Behavioral; Bilateral; Body part; Cell Nucleus; Cells; Cerebral Palsy; Cerebral cortex; Characteristics; Clinical; Contralateral; Data; Digit structure; Distal; Facial Muscles; Flexor; Forelimb; Foundations; Gastrocnemius Muscle; Goals; Hand; Hand functions; Health; Heterogeneity; Hindlimb; Hip region structure; Human; Image; Impairment; Individual; Ipsilateral; Knee; Laboratories; Lateral; Lead; Lower Extremity; Macaca; Maps; Medial; Monkeys; Motor; Motor Activity; Motor Cortex; Motor Neurons; Movement; Movement Disorders; Muscle; Nature; Neurobiology; Neurons; Output; Papio; Patients; Pattern; Positioning Attribute; Posture; Primates; Property; Published Comment; Publishing; Quality of life; Site; Soleus Muscle; Spinal Cord; Spinal cord injury; Stereotyping; Stimulus; Stroke; Synapses; System; Testing; Therapeutic Intervention; Tissues; Transcranial magnetic stimulation; Traumatic Brain Injury; Work; arm; awake; base; conditioning; disability; foot; hemiparetic stroke; joint mobilization; knowledge base; limb movement; monosynaptic reflex; motor deficit; neuromechanism; response; success; ward

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.

描述（由申请人提供）：运动的正常和功能障碍性皮质控制的潜在机制是一个具有重要神经生物学和临床意义的主题。皮质组织的特征已被证明与正常运动以及中风和脑瘫等疾病中的运动障碍直接相关。虽然多年来灵长类动物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，但对下肢的皮质控制知之甚少，尽管其在临床和灵长类动物（包括人类）的运动库中具有明显的重要性。在麻醉猕猴和狒狒的早期研究中，已经建立了后肢运动神经元和初级运动皮层（M1）之间突触联系的一些基本特征，包括单突触连接的存在，这表明突触联系类似于手臂和手部运动神经元。虽然突触学的研究受到一定的限制，但它仍然为清醒灵长类动物的其他功能研究奠定了重要基础。这个建议的总体目标是回答关于后肢皮层控制的功能特性和组织的基本问题，朝着一个更大的目标发展一个知识库，平行于前肢。为实现这一目标，我们提出以下六个具体目标：1）确定与前肢皮层相比，在后肢M1皮层的输出中表示的肌肉协同作用的性质，2）与前肢肌肉表示相比，识别M1后肢肌肉表示的基本特征，3）确定灵长类动物后肢M1皮层与20块后肢肌肉运动神经元之间的突触联系的强度和性质，并与前肢M1皮层的突触联系进行比较，4）表征来自M1皮层的后肢肌肉的刺激触发平均值（StTA）中的突出的晚期易化峰的性质，并确定这些晚期峰背后的神经机制，5）确定与对侧肌肉的作用相比，M1输出对同侧后肢肌肉的作用的特征，和6）使用尖峰和刺激触发的EMG活动平均值来确定猴子M1皮质对快速和慢速踝伸肌的输出效应的性质。与中风、ALS、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导致下肢严重损伤，导致严重残疾和患者生活质量降低。这项建议的重点是描绘功能的正常皮层输出组织下肢肌肉。从这项工作中获得的数据将适用于了解与大脑皮层损伤相关的后肢运动缺陷，并可能提出新的治疗干预策略。