Polyneuronal innervation of skeletal muscle in new‐born rats and its elimination during maturation.

Abstract

SUMMARY1. The events taking place during the elimination of polyneuronal innervation in the soleus muscle of new-born rats have been studied using a combination of electrophysiological and anatomical techniques.2. Each immature muscle fibre is supplied by two or more motor axons which converge on to a single end-plate. There was no sign of electrical coupling between muscle fibres receiving multiple synaptic inputs. By the end of the second week after birth virtually all muscle fibres are innervated by only a single motor axon.3. The average tension produced by individual motor units, measured in terms of the percentage of the total muscle twitch tension, declined dramatically during the first 2 weeks after birth. During this period there was no significant change in the number of motor neurones innervating the soleus muscle. Thus, the disappearance of polyneuronal innervation reflects a decrease in the number of peripheral synapses made by each motor neurone.4. The decline in motor unit size was delayed, but not ultimately prevented, by the early surgical removal of all but a few motor axons to the soleus muscle. This procedure also caused a delay in the removal of polyneuronal innervation involving the remaining motor units.5. Following a crush of the soleus nerve in neonatal animals, regenerating axons usually returned to the original end-plates. Polyneuronal innervation was extensive at early stages of re-innervation and it disappeared during the second week after birth just as in normal muscles. 388 M. C. BROWN, J. K. S. JANSEN AND D. VAN ESSEN end-plates and in most fibres prevented re-innervation by the original nerve. In the small proportion of fibres that did become innervated through both the foreign and original nerves the end-plates were more than 1 mm apart, and both foreign and original nerve end-plates could persist indefinitely.7. Many cross-innervated fibres received multiple inputs through the foreign nerve. Some foreign end-plates were separated by distances ranging up to 1 mm. Polyneuronal innervation through the foreign nerve was completely eliminated during maturation but over a slightly longer period than in normal muscles. Apparently the elimination process can act over a distance up to but not much more than 1 mm.8. These observations suggest that there are several factors influencing the elimination of redundant inputs in immature muscles. Individual motor neurones appear to have an inherent tendency to withdraw the majority of their original complement of peripheral terminals. The determination of which particular synapses are to survive, however, seems to be made in the periphery by a selection among all the synapses that innervate a limited region of each muscle fibre. There may be a competitive interaction among synapses in which those belonging to smaller motor units are less likely to be eliminated, thereby leading to a relatively uniform size of the motor units in the soleus.

El acoplamiento excitación-contracción en el músculo esquelético: preguntas por responder a pesar de 50 años de estudio

“…Siguiendo la secuencia de eventos que ocurren durante el acoplamiento excitación-contracción en fibras musculares adultas de vertebrados, tenemos que, durante el desarrollo posnatal de músculo esquelético de ratones, ocurren principalmente las siguientes modificaciones: i) La desaparición de la inervación polineural entre los días 16 y 18 después del nacimiento (135).…”

Human muscle cultured in monolayer and cocultured with fetal rat spinal cord: importance of dorsal root ganglia for achieving successful functional innervation

“…Loss of multi-endplate status of muscle fibers during development in vivo is a well-recognized phenomenon, (Redfern, 1970;Brown et al, 1976;Dennis et al, 198 1;Bennett, 1983). It has been suggested that, while clustering of AChRs at the nervemuscle contact does not depend on muscle activity, the loss of multi-endplate status and accumulation of AChE may depend on muscle activity (Giacobini et al, 1973;Lomo and Slater, 1978;Rubin et al, 1980;and review in Bennett, 1983).…”

Hormonal regulation of motor unit size and synaptic strength during synapse elimination in the rat levator ani muscle

“…For example, motoneurons initially innervate more muscle fibers, and establish larger motor units, than they do in adulthood (Brown et al, 1976). Consequently, developing mammalian muscle fibers are initially polyneuronally innervated (Redfem, 1970) rather than singly innervated as in adults.…”

“…This was done by measuring the percentage of twitch or tetanus tension of individual motor units relative to the maximal twitch or tetanus tension of the whole muscle. The selective elimination of multiple inputs may involve some form ofcompetition that is mediated via the muscle fiber (Brown et al, 1976;Thompson and Jansen, 1977;Betz et al, 1980Betz et al, , 1990Fladby and Jansen, 1987;Lichtman and Balice-Gordon, 1990). Moreover, synaptic effectiveness may be an important factor in determining the competitive strength of synapses (e.g., Grinnell et al, 1979;Wigston, 1980;Bennett and Lavidis, 1984b;Herrera, 1987, 1988;Herrera and Werle, 1990;Lichtman and Balice-Gordon, 1990).…”

“…Consequently, developing mammalian muscle fibers are initially polyneuronally innervated (Redfem, 1970) rather than singly innervated as in adults. During synapse elimination, motoneurons retract a large portion of their axonal arbor (Bixby,198 1;Riley,198 l), thus reducing the size of motor units (Brown et al, 1976;Betz et al, 1979;Fladby, 1987; Balice-Gordon and Thompson, 1988) until the adult pattern of single innervation is established (reviewed in Van Essen, 1982;Thompson, 1986;Betz, 1987;Jansen and Fladby, 1990). Recent evidence in the androgen-sensitive levator ani (LA) suggests that steroid hormones may be important regulators of synapse elimination (Jordan et al, 1989a(Jordan et al, ,b, 1990.…”