Mechanisms that maintain motoneuron properties

维持运动神经元特性的机制

• 批准号: 6645012
• 负责人: Martin J Pinter
• 金额: $ 5.57万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6645012
• 关键词: acetylcholine; cats; cholinergic receptors; denervation; innervation; motor neurons; neural degeneration; neuromuscular junction; neurotransmitter transport

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.

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属性。当运动神经元通过轴突切开术与肌肉断开时，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联系时，这些特性就恢复正常.这表明与肌肉的突触接触介导了这些相互作用。支持这一点的是以前的证据表明，轴突切断样变化出现在运动神经元，不能释放足够的乙酰胆碱激活任何肌肉纤维。尽管消除了ACh的诱发量子释放，但可以维持正常的脊髓运动神经元电特性，这一事实表明，几乎没有ACh释放就足够了。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如何在神经肌肉接头处完成。我们的工作旨在测试这些相互作用是否需要乙酰胆碱与肌肉上的受体结合，以确定轴突动作电位是否需要恢复这些属性后，再神经支配，以确定如何神经肌肉接头可能会限制恢复运动神经元的属性后，再神经支配，并确定属性的神经肌肉接头指定与运动神经元平行。因此，对肌肉与运动神经元相互作用的深入研究，将有助于对人类运动神经元疾病发病机制和进展的认识。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。