Reciprocal interactions between perisynaptic Schwann cells and regenerating nerve terminals at the frog neuromuscular junction

Abstract

The perisynaptic Schwann cell (PSC) has gained recent attention with respect to its roles in synaptic function, remodeling, and regeneration at the vertebrate neuromuscular junction (NMJ). Here we test the hypothesis that, following nerve injury, processes extended by PSCs guide regenerating nerve terminals (NTs) in vivo, and that the extension of sprouts by PSCs is triggered by the arrival of regenerating NTs. Frog NMJs were double‐stained with a fluorescent dye, FM4‐64, for NTs, and fluorescein isothiocyanate (FITC)‐tagged peanut agglutinin (PNA) for PSCs. Identified NMJs were imaged in vivo repeatedly for several months after nerve injury. PSCs sprouted profusely beginning 3–4 weeks after nerve transection and, as reinnervation progressed, regenerating NTs closely followed the preceding PSC sprouts, which could extend tens to hundreds of microns beyond the original synaptic site. The pattern of reinnervation was dictated by PSC sprouts, which could form novel routes joining neighboring junctions or develop into new myelinated axonal pathways. In contrast to mammals, profuse PSC sprouting in frog muscles was not seen in response to axotomy alone, and did not occur at chronically denervated NMJs. Instead, sprouting coincided with the arrival of regenerating NTs. Immunofluorescent staining revealed that in muscle undergoing reinnervation 4 weeks after axotomy, 91% of NMJs bore PSC sprouts, compared to only 6% of NMJs in muscle that was chronically denervated for 4 weeks. These results suggest that reciprocal interactions between regenerating NTs and PSCs govern the process of reinnervation at frog NMJs: regenerating NTs induce PSCs to sprout, and PSC sprouts, in turn, lead and guide the elaboration of NTs. © 2000 John Wiley & Sons, Inc. J Neurobiol 44: 343–360, 2000

Terminal Schwann Cells Participate in Neuromuscular Synapse Remodeling during Reinnervation following Nerve Injury

“…These sites lose AChR (Grinnell and Do, 1991). In contrast to rodents, the SCs at frog NMJs begin to grow and extend processes away from the synaptic site only after the return of the nerve (Koirala et al, 2000). To the extent that such growth is the cause of SCs abandoning synaptic sites in mouse muscles, then the frog might be expected to have a generally higher percentage of its synaptic sites faithfully reoccupied in contrast to the mouse.…”

Fluorescent Proteins Expressed in Mouse Transgenic Lines Mark Subsets of Glia, Neurons, Macrophages, and Dendritic Cells for Vital Examination

“…Terminal Schwann cells (TSCs), glial cells that cap the nerve terminal at the NMJ, play roles in maintaining and modulating this synapse (Robitaille, 1998;Reddy et al, 2003) and facilitate its repair after nerve injury (Son and Thompson, 1995a,b;Koirala et al, 2000). Vital imaging of nerve terminals and postsynaptic receptors in muscles has been successfully used to obtain new insights into the stability and plasticity of NMJs (Rich and Lichtman, 1989;Balice-Gordon and Lichtman, 1990Walsh and Lichtman, 2003), and we wished to expand such observations to include TSCs.…”

Synapse–Glia Interactions at the Mammalian Neuromuscular Junction

“…Although recent evidence has been obtained at the amphibian NMJ (Herrera et al, 2000;Koirala et al, 2000), most evidence has been obtained at the mammalian NMJ. For instance, processes extended by PSCs after denervation influence the regrowth of motor axons to the muscles and their guidance back to denervated NMJs (Son et al, 1996).…”