Nerve growth and ectopic synapse formation induced by muscle damage in the frog.

Abstract

The effect of muscle damage on nerve growth and ectopic synapse formation in the frog was investigated by bisecting the cutaneus pectoris (c.p.) muscle following implantation of the hypoglossal nerve. Axons from the stump of the implanted nerve grew considerable distances towards the ends of the cut muscle fibres where they formed synapses. In some preparations, c.p. was only partially cut and in these muscles axonal growth from the implanted nerve occurred across intact fibres to reach the cut ends in the damaged area, suggesting the local release of a growth‐stimulating factor. Stimulation of the hypoglossal nerve elicited contraction of the end‐plate‐free half of c.p. The characteristics of these ectopic synapses were similar to those found in a previous study when the hypoglossal nerve innervated the original end‐plates after denervation of c.p. The mean quantal content of the end‐plate potentials (e.p.p.s) was abnormally low, with long latencies between nerve stimulation and the onset of the e.p.p.s and frequent occurrence of multiphasic e.p.p.s in response to single nerve stimulation.

Increase in polyneuronal innervation in frog muscle after muscle injury.

“…In experiments similar to the present ones, the formation and release of a diffusible factor from the damaged frog muscle fibres has been suggested by Sayers & Tonge (1984). They observed that injury to muscle stimulates nerve growth and formation of ectopic synapses by an implanted foreign nerve.…”

“…It was of interest to investigate whether local muscle injury also alters the pattern of frog muscle innervation since it modifies muscle activity, induces extra-junctional sensitivity to ACh and makes muscle fibres receptive to additional foreign innervation (Katz & Miledi, 1961, 1964Miledi, 1963;Sayers & Tonge, 1984).…”

Induction of active zones at ectopic neuromuscular junctions in the frog

“…Since junctional folds are absent in extrasynaptic regions, examining neuromuscular junctions induced at previously endplate-free regions may provide further insights into the differentiation of active zones. Ectopic neuromuscular junctions, complete with nerve terminals and Schwann cells, can be induced de novo in frogs by excising the original endplate sites and implanting the nerve to an endplate-free region of the muscle (Miledi, 1962(Miledi, , 1963Ding, 1982;Sayers and Tonge, 1984). Accumulation of ACh receptors and acetylcholinesterase, and the differentiation of new junctional folds (Korneliussen and Sommerschild, 1976;Lomo and Slater, 1980;Breitschmid and Brenner, 198 1;Weinberg et al, 198 1) are observed in ectopic junctions.…”

“…Accumulation of ACh receptors and acetylcholinesterase, and the differentiation of new junctional folds (Korneliussen and Sommerschild, 1976;Lomo and Slater, 1980;Breitschmid and Brenner, 198 1;Weinberg et al, 198 1) are observed in ectopic junctions. Physiological studies have shown by the presence of spontaneous and evoked endplate potentials that ectopic junctions are functional (Miledi, 1962;Sommerschild, 198 1;Ding, 1982;Sayers and Tonge, 1984). Ding (1982) has shown that quanta1 contents at ectopic junctions are approximately 2.5 times larger than normal.…”