NEURONAL BASIS OF RECOVERY OF A DEFINED MOTOR BEHAVIOR

特定运动行为恢复的神经元基础

• 批准号: 6112284
• 负责人: DONALD S FABER
• 金额: $ 17.76万
• 依托单位: MCP HAHNEMANN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-01 至 2001-07-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6112284
• 关键词: alternatives to animals in research; axon; confocal scanning microscopy; disease /disorder model; electromyography; glia; goldfish; growth cones; immunocytochemistry; nervous system regeneration; neural transmission; neuromuscular function; reticulospinal tract; spinal cord injury; spinal cord surgery; startle reaction

In contrast to adult mammals, axons of goldfish central neurons are capable of regenerating across spinal cord lesions and establishing neuronal circuits that support behavioral recovery. Our long-term goal is to determine mechanisms underlying both the successful regeneration and recovery of function by identified goldfish CNS neurons, in order to develop strategies that will maximize conditions favoring functional recovery from spinal injury in mammals.. For this purpose we use the goldfish Mauthner (M-) cell, an identifiable reticulospinal neuron that mediates a defined behavior, the C-start, and whose inputs and outputs are precisely known. A few months after spinal cord injury, the M-axon regenerates across the lesion, stimulation of the regenerated axon can produce trunk electromyographic responses, and the C-start behavior returns. The experiments proposed here are designed to elucidate the role of the M-axon and its output connections in this behavioral recovery, and to determine if the new connectivity mimic that established normally or whether alternative strategies are adopted. Specific Aim 1 uses behavioral, morphological and electrophysiological measurements to test the hypothesis that the M-cell contributes to the recovery of the C-start behavior following a spinal cord crush. In Specific Aim 2, intracellular recordings will be used as well, to determine if the regenerating M-axon reestablishes functional synapses with motoneurons and/or descending spinal interneurons that synapse with motoneurons. Similarly, in Aim 3 we will correlate the changes in the C-start and in the functional properties of identified supraspinal output synapses of the M-axon with the process of axonal regeneration. Finally, in Aim 4 we will test the hypothesis that nonneuronal cells support regeneration of the M-axon by providing an environment conductive to growth. The results of these studies will provide important insight concerning the clinical problem of the recovery of locomotor function following spinal cord injury.

与成年哺乳动物相反，金鱼中央神经元的轴突能够 跨脊髓病变再生并建立神经元 支持行为恢复的电路。 我们的长期目标是 确定成功再生和 通过已识别的金鱼CNS神经元恢复功能，以便 制定将最大化有利于功能的条件的策略 从哺乳动物中的脊柱损伤中恢复。为此，我们使用 Goldfish Mauthner（M-）细胞，一种可识别的网状脊髓神经元 介导定义的行为，c start，并且其输入和输出为 精确知道。 脊髓损伤几个月后，M轴 在整个病变中再生，刺激再生轴突可以 产生躯干肌电图反应，并产生C启动行为 返回。 此处提出的实验旨在阐明角色 M-Axon及其在此行为恢复中的输出连接，以及 确定是否模仿正常建立的新连接性或 是否采用替代策略。 特定目标1用途 行为，形态学和电生理测量，以测试 假设M细胞有助于恢复C-start 脊髓压伤后的行为。 在特定的目标2中，细胞内 还将使用录音，以确定是否重新生成M-axon 与运动神经元重新建立功能突触和/或降脊柱 与运动神经元突触的神经元。 同样，在AIM 3中，我们将 将C-start的变化和功能特性相关联 MAXON确定了脊柱上的输出突触 轴突再生。 最后，在AIM 4中，我们将检验以下假设。 非神经元细胞通过提供M轴的再生 环境导电到增长。 这些研究的结果将 提供有关恢复临床问题的重要见解 脊髓损伤后的运动功能。