The perinatal reorganization of the innervation of skeletal muscle in mammals.

(1) The perinatal reorganization of muscle innervation is executed in a setting established by the earlier embryonic developmental processes. Prominent among these is the generation of a stereotyped set of skeletal muscles, each innervated in an orderly fashion from an appropriate pool of spinal motoneurons. The muscles contain functionally specialized types of fibers which differentiate in patterns characteristic for each muscle even without innervation. (2) Cholinergic motoneurons are required for functional innervation of skeletal muscles. In addition the muscle fibers must be in a receptive state. Denervation or paralysis recreates the receptive state. Chemically the receptive state is not well defined. It is associated with an immature distribution of AChRs and NCAM. (3) Nmjs are located in an orderly fashion on muscle fibers. Their normal distribution can be disrupted by paralysis during development. When junctions are first formed the nerve terminal induces local aggregation, stabilization and mature ionophore kinetics of the AChRs, as well as appearance of junctional specific AChE. Some of the effects require muscle activity. Terminal-derived substances like agrin and CGRP may normally contribute to these processes, as may other not yet identified agents. (4) Numerically, motoneuronal pools are regulated according to the available target. At the same time, the generation of secondary myotubes requires innervation by active motoneurons, and may also be quantitatively regulated by the number of innervating motoneurons. The generation of the primary generation of myotubes is independent of innervation. (5) Soon after the muscle fiber is first innervated additional terminals from other axons form junctions at the same site. The extent of polyneuronal innervation differs between muscles and between fiber types in the same muscle. Following a delay of several days after birth the individual terminals increase their contact area by arborization. The postsynaptic differentiation with redistribution of AChR, AChE and formation of subsynaptic folds is initiated. The complete maturation of the endplate requires several weeks. (6) Around birth or a few days later processes which eliminate redundant terminals are initiated. The rate of elimination appears to be aimed at nearly synchronous completion of the process in muscles with related functions. (7) There are two types of processes involved in the elimination of supernumerary terminals. The one gives rise to a competitive interaction between terminals innervating the same muscle fiber. The second is related to the reduction in the number of terminals which a motoneuron can maintain in the muscle. The two normally act in concert to determine the mature pattern of innervation of a muscle.(ABSTRACT TRUNCATED AT 400 WORDS)