Control of acetylcholine sensitivity and synapse formation by muscle activity.

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Abstract
The formation of ectopic junctions between the foreign superficial fibular nerve and the soleus muscle of adult rats, and its relation to changes in extrajunctional sensitivity to acetylcholine (ACh), was studied by denervating the muscle 3-6 wk after implanting the foreign nerve. The earliest signs of nerve-muscle transmission were seen 2.5-3 days after denervation, in those fibers where the extrajunctional ACh sensitivity first reached its full post-denervation level. The number of innervated fibers continued to increase throughout the 1st wk after denervation until 70-100% of the fibers underlying the foreign nerve growth were innervated. Direct stimulation of muscles with chronically implanted electrodes from the time of denervation prevented the formation of functional neuromuscular junctions (NMJ). If stimulation began 2 or 4 days after denervation, some functional NMJ were formed which could be detected 7-9 days after denervation, though not as many as in the absence of stimulation. Direct stimulation of muscles from the time of denervation prevented the development of detectable extrajunctional ACh sensitivity. If stimulation began 2 days after denervation nearly maximal sensitivity developed during the 3rd day and then rapidly declined to undetectable levels by the beginning of the 8th day after denervation.