MODULATION OF MOTONEURON OUTPUT IN THE SPINAL CORD

脊髓运动神经元输出的调节

• 批准号: 3397659
• 负责人: ROBERT A DAVIDOFF
• 金额: $ 14.79万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-09-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3397659
• 关键词: Anura; G protein; aminoacid; biological signal transduction; catecholamines; chordate locomotion; electrical potential; electrophysiology; fresh water environment; interneurons; membrane channels; microelectrodes; motor neurons; neural conduction; neural information processing; neuropeptides; neuropharmacology; neurotransmitter receptor; neurotransmitters; norepinephrine; posture; receptor; serotonin; spinal cord; spinal nerves; synapses; thyrotropin releasing hormone

Spinal alpha-motoneurons ("the final common path") translate a large, complex inflow of synaptic signald from segmentsl and descending fibers and interneurons into a precise output neecessary to maintain posture and initiate movement. In particular motoneurons must intergate information from both "fast" trasmitters and "slow" tansmittrs, such as monoamines and peptides which use several different transduction mechanisms ("second messengers") to influence motoneuron excitability. The process is even more complicated becaues "slow" transmitters appear able to modulate the effects of "fast" transmitters. The overall objective of the present investigations is to elucidate some of the complex, interconnected mechanisms by which motoneurons are affected by transmitters putatively released by descending and segmental sources. If dysfunction of synaptic mechanism contorlling motoneurons occurs one would not expect normal spinal cord function. And indeed, abnormalities of motoneuron funcion are imlicated in teh excessive response to passive movement in spasticity, in the absence of reflexes in spinal shock, in the flexor spasms of paraplegia, and in teh pathogenesis of tetanus. Thus, the proposed investigations pertain not only to an imporant area of neurobiology, but are also relevant to understanding the mechanisms of, and ultimately to adequatnely treat, several pathological problems. In exploring synaptic factors taht influence the properties of motoneurons, intra-and extracellular electrophysiological and pharmacological techniques will be used to manipulate and record from frog spinal motoneurons maintained in vitro. These technoiques will be used to test hypotheses taht he output of the motoneuron is governed by compelx pharmacological processes such as the modulatory actions of monoamines and peptides, that these modualtory processes involve multiple receptors and coupling, transduction, and ionic mechanisms, and that jmonoamines and peptides affect the function of mroe classical amino acid transmitters. it is anticipated taht these effeorts will result in a clearer understanding of some of the factors that detrmine how various neurotransmitter and modulator inputs are converted into motoneuron output.

脊髓α运动神经元（“最终共同路径”）翻译 来自segmentsl和segmentl的突触信号的大量、复杂的流入 下行纤维和中间神经元转化为所需的精确输出 保持姿势并开始运动。 尤其 运动神经元必须整合来自两个“快速”发射器的信息 和“慢”传输剂，例如使用单胺和肽 几种不同的转导机制（“第二信使”） 影响运动神经元的兴奋性。 过程更是 复杂，因为“慢”发射器似乎能够调制 “快速”发射机的影响。 总体目标 目前的调查是为了阐明一些复杂的、 运动神经元受到影响的相互关联的机制 发射机可能由下行和分段释放 来源。 如果控制运动神经元的突触机制发生功能障碍 人们不会期望脊髓功能正常。 确实， 运动神经元功能异常与过度运动有关 对痉挛状态下被动运动的反应，在没有 脊髓休克、截瘫的屈肌痉挛中的反射，以及 在破伤风的发病机制中。 因此，拟议的调查 不仅涉及神经生物学的一个重要领域，而且还涉及 与理解机制相关并最终 充分治疗一些病理问题。 在探索影响突触特性的因素时 运动神经元、细胞内和细胞外电生理学和 将使用药理学技术来操纵和记录 来自体外维持的青蛙脊髓运动神经元。 这些 技术将用于测试假设 运动神经元受复杂的药理过程控制，例如 作为单胺和肽的调节作用，这些 调节过程涉及多个受体和偶联， 转导和离子机制，并且单胺和 肽影响mroe经典氨基酸的功能 发射机。 预计这些努力将取得成果 更清楚地了解一些决定如何 各种神经递质和调制器输入被转换成 运动神经元输出。