Inactivity-induced motor nerve terminal sprouting in amphibian skeletal muscles chronically blocked by...

There is a positive correlation between contractile inactivity and the initiation of motor neuron sprouting. However, the exact mechanism responsible for this neuronal growth remains obscure. In a previous study (M. M. Wines and M.S. Letinsky, 1988, J. Neurosci. 8: 3909-3919) we investigated this phenomenon by inducing chronic contractile inactivity of an amphibian muscle by exposure to formamide and found that motor neuron sprouting occurs in the presence of normal pressynaptic transmitter release and propagated muscle fiber action potentials. The present study investigates motor neuron sprouting in response to inactivity produced when neuromuscular transmission is blocked by chronic exposure to alpha-bungarotoxin (alpha-BTX). The alpha-BTX-induced muscle paralysis was maintained for 1-63 days by repetitive application of the toxin to the cutaneous pectoris muscle of adult Rana pipiens. During the chronic alpha-BTX treatment end-plate potentials were reduced below threshold, which therefore removed both muscle fiber action potentials and contractile activity. Our findings showed only terminal sprouting. Also, higher sprouting frequencies (up to 100% of the observed terminals) were observed after chronic alpha-BTX treatment, compared to the sprouting response induced by formamide treatment. In view of our earlier formamide results, these observations suggest that the inhibition of the postsynaptic acetylcholine response, and consequently inhibition of muscle fiber electrical and contractile activity, produces a stronger stimulus to motor neuron sprouting than the presence of contractile inactivity alone coupled with normal synaptic transmission and muscle electrical activity.