Barik Arnab, Li Lei, Sathyamurthy Anupama, Xiong Wen-Cheng, Mei Lin
Department of Neuroscience and Regenerative Medicine and.
Department of Neuroscience and Regenerative Medicine and Department of Neurology, Medical College of Georgia, Augusta University, Augusta, Georgia 30912, and Charlie Norwood Veterans Administration Medical Center, Augusta, Georgia 30904.
J Neurosci. 2016 Sep 21;36(38):9770-81. doi: 10.1523/JNEUROSCI.0174-16.2016.
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.
Neuromuscular junctions (NMJs) are critical for survival and daily functioning. Defects in NMJ formation during development or maintenance in adulthood result in debilitating neuromuscular disorders. The role of Schwann cells (SCs) in NMJ formation and maintenance was not well understood. We genetically ablated SCs during development and after NMJ formation to investigate the consequences of the ablation. This study reveals a critical role of SCs in NMJ formation as well as maintenance.
神经肌肉接头（NMJ）是一种三联突触，由运动神经末梢、突触后肌膜和覆盖神经 - 肌肉接触部位的终末施万细胞（TSC）组成。NMJ的形成需要这三种不同成分之间密切的通讯。与已得到充分表征的神经 - 肌肉相互作用不同，关于施万细胞在NMJ形成和维持中的作用知之甚少。我们发现，小鼠中的施万细胞引导神经末梢至预先形成模式的乙酰胆碱受体（AChR）。在胚胎第8.5天（即神经到达肌细胞簇之前）切除施万细胞，对胚胎第13.5天的无神经AChR簇几乎没有影响，这表明施万细胞对于无神经簇可能不是必需的。在胚胎第12.5天切除施万细胞，此时膈神经接近肌纤维，导致神经诱导的AChR簇更小且数量更少；然而，在胚胎第15.5天切除施万细胞会减小AChR簇的大小，但对簇密度没有影响，这表明施万细胞参与AChR簇的成熟。当在胚胎第15.5天切除施万细胞时，微小终板电位幅度降低，但频率未降低，这表明突触后改变可能先于突触前缺陷出现。最后，在NMJ成熟后的出生后第30天切除施万细胞，导致NMJ碎片化和神经肌肉传递缺陷。施万细胞切除后3天微小终板电位幅度降低，但6天后幅度和频率均降低。总之，这些结果表明施万细胞不仅是NMJ形成所必需的，也是其维持所必需的；并且突触后功能和结构似乎对施万细胞切除更敏感。
神经肌肉接头（NMJ）对于生存和日常功能至关重要。发育过程中NMJ形成的缺陷或成年期的维持缺陷会导致使人衰弱的神经肌肉疾病。施万细胞（SCs）在NMJ形成和维持中的作用尚未得到充分理解。我们在发育过程中和NMJ形成后通过基因手段切除施万细胞，以研究切除的后果。这项研究揭示了施万细胞在NMJ形成以及维持中的关键作用。
