Regulation of Motor Neurons by Postsynaptic Targets

IBN-9724155 PI：CHIU 成熟的神经系统发挥功能很大程度上是因为在适当的神经元组之间建立并维持了正确的突触连接。 尽管我们不完全了解如何建立和维持适当的连接，但很明显，神经元网络需要神经细胞与其突触伙伴之间的双向通信。 邱博士有初步证据表明下游或突触后目标可以“回嘴”并调节支配神经元的特征。 她的实验室生产了一种标记物，可以识别仅在成熟运动神经元（直接控制骨骼肌收缩的特殊神经细胞）中发现的分子。 该分子之所以有趣有几个原因。 首先，它具有很强的选择性，并且仅在该单一细胞群中检测到，这表明该分子必须在此类神经元的功能中发挥重要作用。 其次，它出现在发育的非常晚期，此时运动神经元与肌肉细胞建立了成年连接模式。 第三，它的存在需要目标肌肉的积极反应。 最后，当神经和肌肉之间的通讯中断时，该分子就会丢失。 总之，这些结果表明，当运动神经元形成并维持与肌肉的主动突触接触时，它们获得了任何其他细胞类型中都没有的独特分子。 这些初步结果表明，当肌肉被激活时，它们会向突触前（上游）神经元返回信号；然后，这种逆行信号赋予了仅在运动神经元中发现的生化特性。 通过这种方式，突触后靶标可以调节其神经支配神经元的生化性质。 邱博士现在将研究运动神经元和肌肉之间的通讯如何调节这种分子的水平，她将识别和表征这种新颖的运动神经元特异性分子，以了解其在信号传导和维持神经系统正常接线方面的可能功能。

IBN-9724155 PI: CHIU A mature nervous system functions in large part because correct synaptic connections are made and maintained between the appropriate groups of neurons. Although we do not fully understand how appropriate connections are established and maintained, it is clear that neuronal networks require bi-directional communication between nerve cells and their synaptic partners. Dr. Chiu has preliminary evidence that the downstream or post-synaptic target can "talk back" and regulate the characteristics of the innervating neuron. Her laboratory has produced a marker that recognizes a molecule found only in mature motor neurons (the specialized nerve cells that directly control the contraction of skeletal muscles). This molecule is interesting for several reasons. First, it is very selective and detected only in this single population of cells, suggesting that the molecule must play an important role in the function of this class of neuron. Second, it appears very late in development, at a time when motor neurons establish their adult pattern of connections with muscle cells. Third, its presence requires an active response from the target muscle. Finally, the molecule is lost when communication between nerve and muscle is disrupted. Together, these results demonstrate that when motor neurons form and maintain active synaptic contact with muscles, they acquire a unique molecule not found in any other cell type. These preliminary results suggest that when muscles are activated, they return a signal to the presynaptic (upstream) neuron; this retrograde signal then confers a biochemical property found only in motor neurons. In this manner, the post-synaptic target can regulate the biochemical nature of its innervating neurons. Dr. Chiu will now investigate how communication between motor neuron and muscle regulates the levels of this molecule, and she will identify and characterize this novel, motor neuron-specific molecule to understand its possible functions in signalling a nd maintaining the normal wiring of the nervous system.