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 跨脊髓损伤的再生和建立神经元 支持行为恢复的电路。我们的长期目标是 确定成功再生和 通过已鉴定的金鱼中枢神经系统神经元恢复功能，以便 制定战略，最大限度地创造有利功能的条件 哺乳动物脊椎损伤后的恢复。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 调解定义的行为C-Start，其输入和输出为 确切地说是已知的。脊髓损伤几个月后，M轴突 在损伤处再生，刺激再生的轴突可以 产生躯干肌电反应和C-Start行为 回归。这里提出的实验旨在阐明这一角色。 在这种行为恢复中，M轴突和它的输出连接 要确定新连接是否模仿正常建立的连接，或者 是否采取替代战略。特定目标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-Start的恢复 脊髓挤压后的行为。在特定目标2中，细胞内 也将使用录音来确定再生的M轴突是否 重建与运动神经元和/或下行脊髓的功能性突触 与运动神经元突触的中间神经元。同样，在《目标3》中，我们将 将C-Start和功能特性的变化关联起来 识别M轴突的脊髓上输出突触的过程 轴突再生。最后，在目标4中，我们将检验假设 非神经细胞支持M轴突的再生 有利于生长的环境。这些研究的结果将 对康复的临床问题提供重要的见解 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.