Nerve terminal growth remodels neuromuscular synapses in mice following regeneration of the postsynaptic muscle fiber

Abstract

Muscle fibers degenerate and regenerate in responsetocontractile damage, during aging, andinvarious muscle diseases that weaken the fibers. It is known that degeneration and regeneration of the segment of the postsynaptic fiber produces dramatic alterations in the neuromuscularjunction(NMJ) that form sonthe regenerated fiber, butthemechanisms hereareincompletely understood. We have used a laser microbeamtodamage the postsynaptic fibers atindividual NMJsinthe sternomastoid muscle ofliving young adult mice and then followed the synapses vitally over time using fluorescent proteins expressedinmotor neurons and glial cells and staining ofpostsynaptic acetylcholine receptors. We find, in contrast to previous reports, that the mouse nerve terminal retains contact with the synaptic basal lamina marked by cholinesterase staining even in the absence of the target, showing that this terminal does not require a continuous supply of target-derived molecules for its maintenance. Thus, remodeling of the nerve terminal during the period of target absence does notexplainthe subsequentchangesinthenewNMJ.Rather,weseethatthe synapsebecomes alteredasthenew fibersegment regenerates. Mechanisms for remodeling the synapse include failure of the regenerating muscle fiber to contact the old basal lamina and nerve terminal, growth of the nerve terminal and its glia toward the regenerating fiber, and remodeling of the initial contact as the nerve terminal becomes varicose. © 2011 the authors.