Mechanisms that maintain motoneuron properties

这项研究集中在肌肉和运动神经元之间的相互作用，以维持和调节成年脊髓运动神经元的属性。当运动神经元通过轴突切断与肌肉的连接时，它们的电特性发生了戏剧性的变化。当运动神经元轴突与肌肉重新建立突触联系时，这些特性就会恢复正常。这表明，突触与肌肉的接触介导了这些相互作用。支持这一点的是先前的证据，即运动神经元出现了轴突切断样的变化，无法释放足够的ACh来激活任何肌肉纤维。尽管ACh的诱发量子释放被消除，但脊髓运动神经元的正常电特性仍能保持，这一事实表明，很少的ACH释放可能就足够了。本申请中提出的实验旨在进一步测试运动神经元和肌肉之间的相互作用是如何在神经肌肉连接处完成的。我们的工作旨在测试这些相互作用是否需要ACh与肌肉上的受体结合，确定是否需要轴突动作电位来恢复再神经支配后的这些特性，确定神经肌肉接头如何限制再神经支配后运动神经元特性的恢复，以及确定神经肌肉接头的特性与运动神经元平行指定。希望通过对肌肉与运动神经元相互作用的进一步研究，为了解人类运动神经元病的发病机制和进展做出重要贡献。我们的长期目标是确定成人肌肉和脊髓运动神经元之间营养相互作用的机制。

This research focused on interactions between muscle and motor neurons that maintain and regulate adult spinal motoneuron properties. When motoneurons are disconnected from muscle by axotomy, their electrical properties undergo a dramatic change. When motor neuron axons re- establish synaptic contact with muscle, these properties return to normal. This indicates that synaptic contact with muscle mediates these interactions. Supporting this is previous evidence that axotomy-like changes appear in motoneurons that cannot release sufficient ACh to activate any muscle fibers. The fact that normal spinal motoneuron electrical properties can be maintained despite the elimination of evoked quantal release of ACh from what appears to be most of its motor terminals indicates that very little ACH release may be sufficient. The experiments proposed in this application are designed to test further how the interactions between motor neurons and muscle are accomplished at the neuromuscular junction. Our work is designed to test whether these interactions require ACh binding with receptors on muscle, to determine if axonal action potentials are needed for recovery of these properties after reinnervation, to determine how the neuromuscular junction might restrict recovery of motor neuron properties after reinnervation, and to determine the properties of the neuromuscular junction are specified in parallel with motor neurons. It is hoped that further research of the interactions between muscle and motor neuron will make important contributions to the understanding of the pathogenesis and progression of human motor neuron disease. Our long term goal is to identify the mechanisms that underlie trophic interactions between muscle and spinal motoneurons in the adult.