Mechanisms of elimination, remodeling, and competition at frog neuromuscular junctions

Abstract

Mechanisms governing synapse elimination, synaptic remodeling, and polyneuronal innervation were examined in anatomical and electrophysiological studies of frog neuromuscular junctions. There was a substantial level of polyneuronal innervation in adult junctions and this varied seasonally. Nerve terminal retraction and synapse elimination occurred during normal growth and following reinnervation. Synapse elimination was not inevitable, however. Repeated in vivo observations of some identified junctions showed that polyneuronal innervation could persist for over a year, while at other junctions it arose de novo by terminal sprouting. We concluded that polyneuronal innervation in adult muscles was governed by an equilibrium between processes of retraction and elimination on one hand, and sprouting and synaptogenesis on the other. Other observations revealed that structural remodeling was a common feature of adult junctions. Most often, remodeling involved the simultaneous growth and retraction of different parts of the same junction. The net result was usually junctional growth that, in small frogs, appeared to provide a good match between synaptic size and the electrical demands of transmission. In larger animals, pre- and postsynaptic sizes were not as well matched, providing morphological evidence for a growth-associated decline in synaptic efficacy. Finally, electrophysiology was used to describe some of the functional correlates and consequences of competitive interactions between the terminals of different axons. These results are explained by a hypothetical mechanism that involves trophic support provided by the muscle to the motoneuron, the overall level of nerve-muscle activity, and the synchrony of pre- and postsynaptic activity.

Precision of Reinnervation and Synaptic Remodeling Observed in Neuromuscular Junctions of Living Frogs

“…Specifically, double innervation of neuromuscular junctions falls from ϳ50% shortly after reinnervation to ϳ20% over the next 12 weeks after nerve crush (Herrera and Werle, 1990). Among the reinnervated junctions we observed in vivo, some were found to be doubly innervated at 13 weeks.…”

“…With time, this polyneuronal innervation is reduced by a process similar to developmental synapse elimination, in which motor axons retract some of their connections such that motor unit size and the degree of overlap between motor units are reduced (McArdle, 1975;Rich and Lichtman, 1989). In general, the sartorius muscle of Rana pipiens conforms to this pattern (Werle and Herrera, 1988;Herrera and Werle, 1990). However, ϳ20% of sartorius junctions remain polyneuronally innervated for years after reinnervation .…”

“…Unlike similar synapses in mice (Lichtman et al, 1987;Wigston, 1989;Balice-Gordon and Lichtman, 1990;Hill and Robbins, 1991), frog junctions are highly dynamic even in normal intact muscles Chen et al, 1991;Langenfeld-Oster et al, 1993). Cases of apparent synapse elimination and formation of new polyneuronal innervation have been directly observed in frogs (Herrera and Werle, 1990;Herrera et al, 1991). In addition, synapse replacement, wherein the innervation provided by one nerve terminal is substituted by innervation from another terminal, seems to be common in the pectoralis muscle (supracoracoideus) of Xenopus laevis, in which it can be strongly inferred from physiological measurements (Dunia and Herrera, 1993).…”

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

“…This could occur because androgen influences only one of several mechanisms that may influence synapse elimination (e.g., muscle fiber-mediated competition vs. motoneuronal capacity for synapse maintenance; Brown et al, 1976;Thompson and Jansen, 1977;Fladby and Jansen, 1987;Herrera and Werle, 1990). Alternatively, the timing or dose of androgen treatment may have been inappropriate for a total blockage of synapse elimination.…”

“…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). Since androgen may maintain polyneuronal innervation in the LA by preventing or altering synaptic competition, we wished to evaluate the effect of androgen on synaptic strength in the LA.…”