Schwann Cells in Neuromuscular Junction Formation and Maintenance

Abstract

The neuromuscular junction (NMJ) is a tripartite synapse that is formed by motor nerve terminals, postjunctional muscle membranes, and terminal Schwann cells (TSCs) that cover the nerve-muscle contact. NMJ formation requires intimate communications among the three different components. Unlike nerve-muscle interaction, which has been well characterized, less is known about the role of SCs in NMJ formation and maintenance. We show that SCs in mice lead nerve terminals to prepatterned AChRs. Ablating SCs at E8.5 (i.e., prior nerve arrival at the clusters) had little effect on aneural AChR clusters at E13.5, suggesting that SCs may not be necessary for aneural clusters. SC ablation at E12.5, a time when phrenic nerves approach muscle fibers, resulted in smaller and fewer nerve-induced AChR clusters; however, SC ablation at E15.5 reduced AChR cluster size but had no effect on cluster density, suggesting that SCs are involved in AChR cluster maturation. Miniature endplate potential amplitude, but not frequency, was reduced when SCs were ablated at E15.5, suggesting that postsynaptic alterations may occur ahead of presynaptic deficits. Finally, ablation of SCs at P30, after NMJ maturation, led to NMJ fragmentation and neuromuscular transmission deficits. Miniature endplate potential amplitude was reduced 3 d after SC ablation, but both amplitude and frequency were reduced 6 d after. Together, these results indicate that SCs are not only required for NMJ formation, but also necessary for its maintenance; and postsynaptic function and structure appeared to be more sensitive to SC ablation.

4‐Aminopyridine attenuates muscle atrophy after sciatic nerve crush injury in mice

“…Skeletal muscle function is also intimately related to neuromuscular junction (NMJ), and NMJ consists of presynaptic nerve terminal, postsynaptic muscle fiber rich in acetylcholine receptors, and terminal Schwann cells (TSC; or perisynaptic Schwann cells ). Terminal Schwann cells (nonmyelinating SCs) have been reported to be an integral and essential component of NMJ, and several studies have reported that TSCs play an important role in the development, function, maintenance, and regulation of NMJs . Terminal Schwann cells are dynamic after acute nerve injury, and cytoplasmic processes from TSCs serve as platforms for axonal growth and nerve regeneration.…”

“…Terminal Schwann cells (nonmyelinating SCs) have been reported to be an integral and essential component of NMJ, and several studies have reported that TSCs play an important role in the development, function, maintenance, and regulation of NMJs. 36,[56][57][58][59][60][61][62][63] Terminal Schwann cells are dynamic after acute nerve injury, and cytoplasmic processes from TSCs serve as platforms for axonal growth and nerve regeneration. Terminal Schwann cells also modulate activitydependent neurotransmitter release and neurotransmission.…”

NMJ maintenance and repair in aging

“…Exemplifying this point, the loss of the presynaptic or postsynaptic site in adulthood resulting from diseases and injuries causes the NMJ to degenerate [59]. The NMJ fragments and malfunctions within a few days after Schwann cells, including PSCs, are ablated [60]. Conversely, these three cellular components collaborate through synapse-associated molecules to regenerate adult NMJs following injuries that cause severing of motor axons, loss of PSCs and atrophy of muscle fibers [27].…”

Schwann cells participate in synapse elimination at the developing neuromuscular junction

“…Given the ability of tSCs to influence nerve growth and their location at the endplates of developing muscles, investigators have been interested in whether tSCs might play a role in synapse elimination [12,26,27]. Smith et al [27] conducted a detailed light and electron microscopic study of this issue.…”