The Formation and Loss of Supernumerary Synapses in Mammalian Skeletal Muscle

Physiological and anatomical techniques have been employed to investigate the elimination of polyneuronal innervation in skeletal muscles of the neonatal rabbit. In an initial study involving intracellular recording and in vitro tension measurements, it was discovered that different muscles in the rabbit differ with respect to the extent of multiple innervation and the time course of synapse elimination, in a way that suggests a body-wide gradient of neuromuscular development. Counts were then made of both α-motor neurons (using retrograde transport of horseradish peroxidase) and muscle fibers for each of three rabbit muscles, to see whether the differences between muscles in the degree of multiple innervation and/or the rate of synapse elimination were related to the differences in the motor neuron:muscle fiber ratio (the innervation ratio). The results suggest that individual motor neurons from muscles with a 10-fold range of innervation ratios tend initially to establish the same number of synapses, which results in different degrees of multiple innervation among muscles. The rate of synapse elimination in a muscle, however, does not appear to depend on the innervation ratio. An electron microscopic study on the morphological correlates of synapse elimination yielded three main findings: one, synapse elimination appears to involve retraction rather than degeneration of synapses; two, myelination of the pre-terminal axons seems to proceed independently of the loss of synapses; and three, synapses in neonatal muscle can exhibit unusual morphology indicative of their rapidly changing state. A related study was carried out on adult rat muscle. Physiological and anatomical evidence was found that a foreign nerve transplanted onto a muscle with intact innervation is capable of forming and maintaining connections, if its axons grow to the sites of original nerve synapses.