The transneuronal induction of sprouting and synapse formation in intact mouse muscles.

The pattern of innervation to intact peroneal and extensor digitorum longus muscles of normal and experimental young adult mice was studied by light microscopy after staining neuromuscular junctions by a combined silver-cholinesterase stain. Spontaneous sprouting and synapse formation occur in intact muscles of normal mice. In about 7% of the junctions, sprouts contribute to the innervation of muscle fibres already innervated by their parent axons. Axotomy of the sciatic nerve in one hind limb is followed by an average 3-fold increase over normal in the incidence of sprouting and synapse formation in the intact muscles of the opposite hind limb. The time to onset of sprouting and synapse formation becomes shorter as the site of the contralateral axotomy is placed closer to the spinal cord. A significant increase over normal in the incidence of sprouting is first observed 5 days after a proximal sciatic nerve cut and only 12 days after a distal sciatic nerve cut. The timing of sprouting is independent of the difference in the number of axons that are involved in the contralateral axotomies at different sites. These findings suggest that, in the intact muscles of normal mice, sprouting and synapse formation is an ongoing process which can be enhanced by contralateral axotomy. As in frogs (Rotshenker, 1979, 1982) the underlying mechanism may be the transneuronal induction of sprouting and synapse formation.