Control of acetylcholine sensitivity and synapse formation by muscle activity.

1. 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), has been studied by denervating the muscle 3-6 weeks after implanting the foreign nerve. 2. The earliest signs of nerve-muscle transmission were seen 2.5-3 days after denervation, in those fibres where the extrajunctional ACh sensitivity first reached its full post-denervation level. The number of innervated fibres continued to increase throughout the first week after denervation until 70-100% of fibres underlying the foreign nerve growth were innervated. 3. Direct stimulation of muscles with chronically implanted electrodes from the time of denervation prevents the formation of functional neuromuscular junctions (n.m.j.s). If stimulation begins 2 or 4 days after denervation, some functional n.m.j.s are formed which can be detected 7-9 days after denervation, though not as many as in the absence of stimulation. 4. Direct stimulation of muscles from the time of denervation prevents the development of detectable extrajunctional ACh sensitivity. If stimulation begins 2 days after denervation nearly maximal sensitivity develops during the third day and then rapidly declines to undetectable levels by the beginning of the eight day after denervation.