Mechanisms that maintain motoneuron properties

本研究的重点是肌肉和运动神经元之间的相互作用，维持和调节成人脊髓运动神经元的特性。当运动神经元通过轴切断术与肌肉分离时，它们的电特性会发生巨大的变化。当运动神经元轴突与肌肉重新建立突触接触时，这些特性恢复正常。这表明与肌肉的突触接触介导了这些相互作用。支持这一观点的是先前的证据，即运动神经元出现了类似闭锁术的变化，不能释放足够的乙酰胆碱来激活任何肌肉纤维。尽管脊髓运动神经元的大部分运动末端的乙酰胆碱诱导量释放被消除，但正常的脊髓运动神经元电特性仍能维持，这表明很少的乙酰胆碱释放可能就足够了。本应用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与肌肉受体结合，确定轴突动作电位是否需要在神经再生后恢复这些特性，确定神经肌肉连接如何限制运动神经元特性的恢复，并确定神经肌肉连接的特性与运动神经元并行指定。希望对肌肉与运动神经元相互作用的进一步研究将对了解人类运动神经元疾病的发病机制和进展作出重要贡献。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.