A physiological correlate of disuse-induced sprouting at the neuromuscular junction

Abstract

Recent investigations have established that many of the normal properties of muscle fibres are maintained, at least in part, by muscle activity. Thus, a fall in resting membrane potential, an increase in input resistance, and spread of acetylcholine receptors to extrajunctional sites can all be induced by abolishing muscle activity and prevented by direct stimulation of denervated muscle fibres. Muscle activity also exerts a trophic influence on the innervating motoneurones; furthermore it may be a factor in the regulation of sprouting. Brown and Ironton found fine, "ultra-terminal sprouts" emanating from the endplates of muscles rendered inactive by chronic conduction block of the muscle nerve. Pestronk and Drachman saw increased branching of the motor nerve terminal and a consequent increase in endplate size in similar conditions. If these sprouts at the endplates of inactive muscles were functional, one might expect more transmitter to be released in response to nerve stimulation. We report here that both quantum content and spontaneous miniature endplate potential (m.e.p.p) frequency are increased at the terminals of inactive (disused) muscles.

Decreased Synaptic Activity Shifts the Calcium Dependence of Release at the Mammalian Neuromuscular JunctionIn Vivo

“…1 A). This observation was surprising, given previous reports of increases in quantal contents after block of nerve activity with TTX (Snider and Harris, 1979;Tsujimoto and Kuno, 1988;Tsujimoto et al, 1990). However, previous studies were performed with endplates bathed in solution containing low external Ca 2ϩ -raised Mg 2ϩ , and, when we reproduced those conditions, we found a significant increase in quantal content ( Fig.…”

“…More than 25 years ago, it was shown that block of activity at the mammalian neuromuscular junction in vivo increased synaptic strength (Snider and Harris, 1979;Tsujimoto and Kuno, 1988;Tsujimoto et al, 1990). Recent studies have found that a similar increase in synaptic strength occurs after block of activity at synapses between neurons (Manabe et al, 1989;Webb and Cope, 1992;Davis and Bezprozvanny, 2001;Burrone and Murthy, 2003;Turrigiano and Nelson, 2004).…”

“…Such an increase in synaptic strength is homeostatic, because it opposes the reduction of postsynaptic activity. Both increased quantal size (O'Brien et al, 1998;Turrigiano et al, 1998) and increased quantal content (Snider and Harris, 1979;Tsujimoto and Kuno, 1988;Tsujimoto et al, 1990;Murthy et al, 2001) contribute to homeostatic regulation of synaptic strength. Our study focused on the mechanism underlying homeostatic increases in quantal content.…”

“…The simplicity of the preparation allows for easy differentiation between changes in synaptic strength that are caused by changes in quantal size versus changes in quantal content. The first report of what would now be termed homeostatic regulation of synaptic strength came from a study at the neuromuscular junction (Snider and Harris, 1979). In that study, an increase in quantal content was found after block of synaptic activity.…”

Ciliary neurotrophic factor is not required for terminal sprouting and compensatory reinnervation of neuromuscular synapses: Re-evaluation of CNTF null mice

“…These sprouts add or restore synaptic contacts on inactive (Snider and Harris, 1979,Angaut-Petit et al, 1990,Meunier et al, 2002 or denervated muscle fibers, which improve the motor deficits associated with peripheral nerve injury (Brown et al, 1981,Wernig and Herrera, 1986,Tam and Gordon, 2003a or spinal cord injury (Yang et al, 1990,Marino et al, 1994,Thomas et al, 1997. Despite its significance for repair of the adult nervous system, the molecular and cellular events leading to the compensatory process remain elusive.…”