Regulation of Motor Neurons by Postsynaptic Targets

突触后靶标对运动神经元的调节

• 批准号: 9724155
• 负责人: Arlene Chiu
• 金额: $ 33.12万
• 依托单位: Beckman Research Institute City of Hope
• 依托单位国家: 美国
• 项目类别: Continuing grant
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-15 至 1999-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9724155&HistoricalAwards=false
• 关键词: Regulation; Motor; Neurons; Postsynaptic; Targets

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.

IBN-9724155 主要研究者：一个成熟的神经系统的功能在很大程度上是因为正确的突触连接，并保持适当的神经元组之间。 虽然我们还不完全了解适当的连接是如何建立和维持的，但很明显，神经元网络需要神经细胞及其突触伙伴之间的双向通信。 邱博士有初步证据表明，下游或突触后靶点可以“交谈”并调节支配神经元的特性。 她的实验室已经产生了一种标记物，可以识别仅在成熟运动神经元（直接控制骨骼肌收缩的专门神经细胞）中发现的分子。 这个分子很有趣有几个原因。 首先，它是非常有选择性的，并且只在这一单一的细胞群中被检测到，这表明该分子必须在这类神经元的功能中发挥重要作用。 第二，它出现在发育的晚期，此时运动神经元与肌肉细胞建立了成年模式的连接。 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交流中断时，这种分子就会丢失。 总之，这些结果表明，当运动神经元形成并保持与肌肉的活跃突触接触时，它们获得了一种在任何其他细胞类型中都没有发现的独特分子。 这些初步结果表明，当肌肉被激活时，它们向突触前（上游）神经元返回信号;这种逆行信号随后赋予了一种仅在运动神经元中发现的生化特性。 以这种方式，突触后靶标可以调节其支配神经元的生化性质。 Chiu博士现在将研究运动神经元和肌肉之间的通信如何调节这种分子的水平，她将鉴定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布线中的可能功能。