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.
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