NEURONAL BASIS OF RECOVERY OF A DEFINED MOTOR BEHAVIOR

与成年哺乳动物相比，金鱼中枢神经元的轴突能够 在脊髓损伤处再生， 支持行为恢复的回路 我们的长期目标是 确定成功再生的机制， 通过鉴定的金鱼CNS神经元恢复功能， 制定战略，将最大限度地有利于功能的条件 从哺乳动物的脊髓损伤中恢复过来 为此，我们使用 金鱼Mauthner（M-）细胞，一种可识别的网状脊髓神经元， 中介一个定义的行为，C-start，其输入和输出是 精确地知道。 脊髓损伤后几个月， 再生的轴突，刺激再生的轴突， 产生躯干肌电反应和C-启动行为 回报. 这里提出的实验旨在阐明 在这个行为恢复过程中的M-轴突及其输出连接， 以确定新的连接是否模仿正常建立的连接，或者 是否采用替代策略。 具体目标1用途 行为、形态和电生理测量，以测试 假设M细胞有助于C启动的恢复 脊髓损伤后的行为 在特定目标2中，细胞内 也将使用记录，以确定再生的M-轴突是否 重建与运动神经元和/或下行脊髓神经元的功能性突触 与运动神经元形成突触的中间神经元。 同样，在目标3中，我们将 将C-启动的变化与 识别出M-轴突的脊髓上输出突触， 轴突再生 最后，在目标4中，我们将检验以下假设： 非神经元细胞通过提供一个神经元受体来支持M-轴突的再生。 有利于生长的环境。 这些研究的结果将 提供了关于恢复的临床问题的重要见解 脊髓损伤后的运动功能。

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.