Spinal Neuron Excitability During Voluntary Movement

描述(申请人提供)：拟议的实验是一项研究工作的组成部分，其长期目标是了解脊髓在控制灵长类手臂自主运动中所起的作用。这一目标包括寻找治疗或干预措施，以克服与脊髓损伤相关的运动障碍。这项拟议的研究通过阐明控制正常行为猴子前臂运动的脊髓中间神经元的功能组织来推进这些目标。在对运动损伤和损伤后恢复的研究进行有用的解释之前，彻底了解正常的脊髓功能是必不可少的。该项目的具体目标是：1.位于颈椎膨大吻侧的固有脊髓中间神经元在控制灵长类动物手臂和手的运动中起什么作用？2.在正常运动中，运动神经元和中间神经元的兴奋性是如何被脊髓中的抑制机制调节的？3.自由运动中脊髓运动神经元的正常活动是否依赖于单胺类的作用？在清醒的猴子中，颈部神经元的活动将在自主伸展、孤立的手腕运动以及腕屈伸肌的共同收缩过程中被记录下来。脊髓神经元的抑制性和神经调节剂的输入将通过局部离子导入来操纵，这些药物可以激活或阻断5-羟色胺、去甲肾上腺素、GABA或甘氨酸受体。中间神经元的输入和输出连接将通过尖峰触发的EMG平均值以及对外周传入和下行通路的自然和电刺激来识别。这些研究将阐明在自主运动中控制中间神经元和运动神经元兴奋性的机制，并为进一步研究运动功能障碍和损伤后恢复的机制奠定基础。

DESCRIPTION (provided by applicant): The proposed experiments are components of a research effort whose long-term objective is to understand the role played by the spinal cord in the control of voluntary movements of the primate arm. This goal includes a search for therapies or interventions that will overcome the motor deficits associated with spinal cord injury. The proposed study advances these goals by elucidating the functional organization of spinal interneurons controlling forearm movements in the normal, behaving monkey. A thorough understanding of normal spinal function is essential before studies of motor impairment and recovery following injury can be interpreted usefully. The specific aims of the project are: 1. What is the role of propriospinal interneurons located rostral to the cervical enlargement in the control of primate arm and hand movements? 2. How are motoneuron and interneuron excitability regulated during normal movements by inhibitory mechanisms in the spinal cord? 3. Is the normal activity of spinal motoneurons during voluntary movement dependent on the action of monoamines? The activity of cervical neurons will be recorded during voluntary reaching, isolated wrist movements, and cocontraction of flexor and extensor muscles of the wrist in the awake monkey. Inhibitory and neuromodulator inputs to spinal neurons will be manipulated with local iontophoresis of pharmacological agents that activate or block serotonin, noradrenaline, GABA or glycine receptors. Input and output connections of interneurons will be identified with spike-triggered averages of EMG and natural and electrical stimulation of peripheral afferents and descending pathways. These studies will elucidate the mechanisms by which the excitability of interneurons and motoneurons are controlled during voluntary movements and lay the foundation for future studies on the mechanisms of motor dysfunction and recovery from injury.