The role of postsynaptic muscle fibers in maintenance and repair of mammalian neuromuscular junctions

by Li, Yue

In order to examine how terminal Schwann cells and nerve terminals respond to muscle fiber damage, I conducted vital imaging experiments in which I damaged individual muscle fibers with a laser microbeam and examined the response of GFPexpressing Schwann cells and CFP-expressing motor axons during muscle fiber degeneration and regeneration in transgenic mice. In the course of these experiments, I noted an unexpected persistence of the alignment of synaptic components. Two days after muscle fiber damage, the synaptic site was obviously shrunken, presumably due to the loss of the underlying muscle fiber. Acetylcholine receptors labeled with bungarotoxin prior to fiber ablation, although more faintly labeled, persisted afterwards. The arborization of the terminal Schwann cells (TSCs) and the nerve terminals also were shrunken, but not obviously changed in their branching pattern. Even 4 days after fiber 17 damage, near the time when a newly regenerated fiber is sometimes seen within the sheath of the previous fiber, some of the old (bungarotoxin-labeled) receptors were still visible at the original synaptic sites (they can last for months). Additionally, nerve terminals and Schwann cells had neither retracted nor extended from the synaptic site. All these observations suggest that as a muscle fiber degenerates following extrasynaptic damage, the synaptic components, including some persistent AChR remain in alignment. This implies that this synaptic alignment has structural components that persist following loss of the postsynaptic muscle fiber and the changes in synaptic signaling that must result.