TRANSMISSION MODES & THEIR MEDIATORS IN MOTONEURONS

这项计划的长远目标是改善 对路径、发射机和发射机的理解 一种机制，通过它将脉冲从 运动神经元(MN)的突触前输入。瘦(500微米) 脊髓横断切片及其相应的背侧和 腹侧神经根取自胸腰椎节段 新生(12-18天)大鼠脊髓，在 风琴浴缸。蜂窝内录音将从 逆序识别的MN。传导速度 将计算逆行尖峰，以进一步确定 有问题的神经元是一个MN。第一，被动和主动 α和伽马MN的膜性质将是 特色化的。第二，突触电位将由 用双极电刺激背根中的任一个 电极或通过在100-200微米以外的地方进行焦点刺激 被刺穿的NM。波形、时间进程、输入电阻 诱发电位的变化、翻转电位及其离子机制 将对突触电位进行分析。第三，作为我们的初步工作 结果表明，去极化和超极化都是 具有几秒到几分钟的时间进程的突触电位可以 从MN的电生理特征中诱发出 这些慢电位将被研究。第四，法律制度的性质 负责快慢突触电位的递质 将使用药理拮抗剂进行系统分析 已知的和假定的传递体，包括兴奋性和 抑制性氨基酸、生物胺和多肽。最后， 可能作为传递体的内源性物质 对于快和慢突触电位，如谷氨酸， 天冬氨酸、多肽(P物质、促甲状腺激素释放激素、 脑啡肽等)和胺(去甲肾上腺素、肾上腺素、 5-羟色胺等)将通过灌流或 压力喷射以确定这些化合物是否 模仿快速和慢速突触电位。这项建议 构成了第一次系统地尝试定义和 针对MN的各种传输模式和 它们的化学介体。这一知识对我们的 对脊髓功能和功能障碍的认识 并用于设计治疗多种神经系统疾病的药物 脊髓的紊乱；例如。计划中的研究可能会澄清 促甲状腺激素释放激素治疗的机制 治疗肌萎缩侧索硬化症并帮助开发更好的药物 或治疗方案。

The long range objective of this project is to improve understanding of the pathways, transmitters and transmitter mechanisms by means of which impulse is transmitted from the presynaptic inputs to the motoneurons (MN's). Thin (500 mum) transverse spinal cord slices with their corresponding dorsal and ventral rootlets will be obtained from thoracolumbar segments of neonatal (12-18 days old) rat spinal cord and maintained in an organ bath. Intracellular recordings will be made from antidromically identified MN's. The conduction velocity of antidromic spikes will be calculated to further establish that the neuron in question is a MN. First, the passive and active membrane properties of alpha and gamma MN's will be characterized. Second, synaptic potentials will be induced from MN's by either stimulation of dorsal rootlets with a bipolar electrode or by focal stimulation 100-200 mum away from the impaled NM. The waveform, time course, input resistance change, reversal potential and the ionic mechanism of evoked synaptic potentials will be analyzed. Third, as our preliminary results have shown that both depolarizing and hyperpolarizing synaptic potentials with a time course of seconds to minutes can be evoked from MN's the electrophysiological characteristics of these slow potentials will be investigated. Fourth, the nature of transmitters responsible for the fast and slow synaptic potentials will be systematically analyzed using pharmacological antagonists to known and putative transmitters including excitatory and inhibitory amino acids, biogenic amines and peptides. Lastly, endogenous substances which are likely to serve as transmitters for the fast and slow synaptic potentials such as glutamate, aspartate, peptides (substance P, thyrotropin releasing hormone, enkephalins, etc.) and amines (norepinephrine, epinephrine, serotonin, etc.) will be applied to MN's by either superfusion or pressure ejection to determine whether or not these compounds mimic the fast and slow synaptic potentials. This proposal constitutes the first systematic attempt to define and characterize for the MN's the various transmission modes and their chemical mediators. This knowledge is central to our understanding of the function and dysfunction of the spinal cord and for the design of drugs in the treatment of many neurological disorders of the spinal cord; eg. the projected study may clarify the mechanism underlying thyrotropin releasing hormone therapy of amyotrophic lateral sclerosis and help developing better drugs or therapeutic regimens.