MODULATION OF MOTONEURON OUTPUT IN THE SPINAL CORD

脊髓运动神经元输出的调节

• 批准号: 2263227
• 负责人: ROBERT A DAVIDOFF
• 金额: $ 15.82万
• 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/2263227
• 关键词: Anura; G protein; alternatives to animals in research; 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.

脊柱α------------“最终公共路径”）翻译 来自segmentsl和 将纤维和中间神经元降为必要的精确输出 保持姿势并引发运动。 尤其 运动神经元必须从两个“快速”示威器中交叉信息 和“慢”的Tansmittrs，例如单胺和使用的肽 几种不同的转导机制（“第二使者”） 影响运动神经元的兴奋性。 该过程甚至更多 复杂的，因为“慢”发射器似乎能够调节 “快速”发射器的影响。 总体目标 目前的研究是为了阐明某些复合物 运动神经元受影响的互连机制 发射器通过下降和分段发布 来源。 如果突触机制的功能障碍发生，则发生运动神经元 人们不会期望正常的脊髓功能。 确实， 运动神经元功能的异常在过多 在没有痉挛中对被动运动的反应 脊柱冲击中的反射，截瘫的屈曲痉挛和 在破伤风的发病机理中。 因此，拟议的调查 不仅与神经生物学的重要领域有关，而且也是 与理解的机制有关，并最终与 充分治疗，几个病理问题。 在探索突触因子时，taht影响了 运动神经元，细胞外电生理学和 药理技术将用于操纵和记录 从青蛙脊柱运动神经元中维持体外。 这些 技术将用于检验假设的输出 Motoneuron受刺激性药理学过程的约束 作为单胺和肽的调节作用， 模拟过程涉及多个受体和耦合， 转导和离子机制，以及Jmonoamines和 肽会影响MROE经典氨基酸的功能 发射器。 预计这些Effeorts会导致 在更清楚地理解某些因素的因素中 各种神经递质和调节器输入被转换为 Motoneuron输出。