Analysis of Mechanisms for the Formation of Nerve Terminal Sprouts

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Sprouting of nerve terminals has been assumed to be a morphological correlate of plastic changes in functional synaptic transmission. To test this assumption, we induced sprouting of motor nerve terminals in the rat extensor digitorum longus muscle by chronic conduction block of the sciatic nerve with tetrodotoxin. The amount of transmitter release at these neuromuscular junctions was measured electrophysiologically in terms of the mean quantum content of end-plate potentials., When the nerve conduction had been blocked for 6 days, about 35% of the motor nerve terminals examined in the hind leg muscle showed sprouting. After measurements of transmitter release by electrophysiological experiments, each muscle fiber was stained with fluorescent dye, and the same neuromuscular junctions were used for morphometric observations. Following a conduction block of the sciatic nerve for 6 days, all the neuromuscular junctions showed a significant increase in the amount of transmitter release uni … More formly, regardless of the presence or absence of terminal sprouts. The total terminal length in the junctions with sprouts was significantly greater than that in those without sprouts. However, there was no correlation between the terminal length and the amount of transmitter release. It is concluded that terminal sprouting and increased transmitter release are not causally related.We have previously shown that the formation of terminal sprouts at neuromuscular junctions is significantly inhibited by treatment with calcitonin gene-related peptide (CGRP). This suggests that CGRP may be transported from the neuron cell body to its terminal in which CGRP may act as a neurotrophic factor. To test this possibility, we developed a highly sensitive enzyme immunoassay for CGRP. With this assay, the CGRP content in the sciatic nerve was found to be about 100 pg/mm. Also, about 95% of CGRP detected in skeletal muscle was found to originate from neural tissues. In both the peripheral sensory and motor nerve fibers, CGRP was found to transport in the somatofugal direction at a rate of about 1 mm/hr. Less