TY - JOUR
T1 - Schwann cells in neuromuscular junction formation and maintenance
AU - Barik, Arnab
AU - Li, Lei
AU - Sathyamurthy, Anupama
AU - Xiong, Wen Cheng
AU - Mei, Lin
N1 - Funding Information:
This study was supported in part by Grants from the National Institutes of Health and Veterans Affairs. L.M. is a Georgia Research Alliance Eminent Scholar in Neuroscience.
Publisher Copyright:
© 2016 the authors.
PY - 2016/9/21
Y1 - 2016/9/21
N2 - 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 alterationsmayoccur ahead of presynaptic deficits. Finally, ablation of SCs at P30, afterNMJmaturation, 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 forNMJ formation, but also necessary for its maintenance; and postsynaptic function and structure appeared to be more sensitive to SC ablation.
AB - 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 alterationsmayoccur ahead of presynaptic deficits. Finally, ablation of SCs at P30, afterNMJmaturation, 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 forNMJ formation, but also necessary for its maintenance; and postsynaptic function and structure appeared to be more sensitive to SC ablation.
KW - AChRs
KW - Glia
KW - NMJ
KW - Schwann cell
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U2 - 10.1523/JNEUROSCI.0174-16.2016
DO - 10.1523/JNEUROSCI.0174-16.2016
M3 - Article
C2 - 27656017
AN - SCOPUS:84988474357
SN - 0270-6474
VL - 36
SP - 9770
EP - 9781
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 38
ER -