Cortical Control of Hindlimb Muscles in Primates

灵长类动物后肢肌肉的皮质控制

• 批准号: 7565455
• 负责人: PAUL DAVID CHENEY
• 金额: $ 38.93万
• 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/7565455
• 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; Goals; Hand; Hand functions; Heterogeneity; Hindlimb; Hip region structure; Human; Image; Impairment; Individual; Ipsilateral; Joints; 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; Upper arm; Work; awake; base; conditioning; disability; foot; hemiparetic stroke; knowledge base; limb movement; monosynaptic reflex; motor deficit; neuromechanism; public health relevance; 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）：正常和功能失调的皮层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运动障碍的各个方面直接相关。虽然灵长类动物手臂和手的皮质控制多年来一直是人们广泛关注的焦点和大量研究的主题，但人们对下肢的皮质控制知之甚少，尽管它在临床和包括人类在内的灵长类动物的运动技能方面具有明显的重要性。对麻醉猕猴和狒狒的早期研究已经确定了后肢运动神经元和初级运动皮层（M1）之间突触连接的一些基本特征，包括单突触连接的存在，表明突触连接类似于手臂和手运动神经元的突触连接。尽管突触学方面的工作受到一定限制，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。该提案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，以实现开发与前肢平行的知识库的更大目标。为了实现这一目标，我们提出以下六个具体目标：1）与前肢皮层相比，确定后肢 M1 皮层输出中所表示的肌肉协同作用的特性；2）与前肢肌肉表示相比，确定 M1 后肢肌肉表示的基本特征；3）确定灵长类动物后肢 M1 皮层到灵长类动物后肢 M1 皮层的突触联系的强度和性质。 20 个后肢肌肉的运动神经元与前肢 M1 皮层的运动神经元进行比较，4) 表征 M1 皮层后肢肌肉刺激触发平均值 (StTA) 中突出的晚期促进峰的特性，并确定这些晚期峰背后的神经机制，5) 确定 M1 输出对同侧后肢影响的特征 6) 使用脉冲和刺激触发的 EMG 活动平均来确定猴子 M1 皮层到快速和慢速踝伸肌的输出效应的性质。公共卫生相关性 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，导致严重残疾并降低患者的生活质量。该提案的重点是描绘下肢肌肉的正常皮质输出组织的特征。这项工作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，并可能提出新的治疗干预策略。