The molecular physiology of the axo-myelinic synapse
The molecular physiology of the axo-myelinic synapse
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DOI：
10.1016/j.expneurol.2015.10.006
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发表时间：
2016-02-01
影响因子：
5.3
通讯作者：
Stys, Peter K.
中科院分区：
文献类型：
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作者：
Micu, Ileana;Plemel, Jason R.;Stys, Peter K.
髓鞘轴突有效地长距离传递信息。相对的髓鞘赋予有利的电特性，但限制轴突进入其细胞外环境。因此，轴突代谢支持可能需要特定的轴-髓鞘通讯。在这里，我们探索了活动依赖的谷氨酸介导的信号从轴突到髓鞘。2光子显微镜用于成像Ca2+髓鞘的变化，以响应视神经轴突的电刺激离体。我们发现视神经髓磷脂响应轴突动作电位的升高Ca2+水平由GluN2D和giun3a -含NMDA受体介导。谷氨酸以水泡的方式从轴突释放，对破伤风毒素敏感。囊泡融合的Ca2+来源是由轴突Ca2+储存上的ryanodine受体提供的，由l型Ca2+通道控制，该通道感知结间轴膜的去极化。基因消融GluN2D和GIuN3A亚基导致致密髓磷脂更大的不稳定性。我们的研究结果支持轴突和髓鞘之间存在一种新的突触，表明通过这种突触，穿越的动作电位可以向上覆的髓鞘发出信号。这可能是一个重要的生理机制，通过轴突向伴生胶质细胞发出信号，以动态方式支持其代谢或调节其髓磷脂的特性。轴-髓鞘突触可能有助于学习，而其紊乱可能在中枢神经系统疾病（如精神分裂症）的病理生理学中发挥作用，在这种疾病中，有髓鞘白质束的细微异常已经在人类中被显示出来，或者是直白的脱髓鞘疾病（如多发性硬化症）。(C) 2015爱思唯尔公司版权所有。
Myelinated axons efficiently transmit information over long distances. The apposed myelin sheath confers favorable electrical properties, but restricts access of the axon to its extracellular milieu. Therefore, axonal metabolic support may require specific axo-myelinic communication. Here we explored activity-dependent glutamate-mediated signaling from axon to myelin. 2-Photon microscopy was used to image Ca2+ changes in myelin in response to electrical stimulation of optic nerve axons ex vivo. We show that optic nerve myelin responds to axonal action potentials by a rise in Ca2+ levels mediated by GluN2D and GIuN3A-containing NMDA receptors. Glutamate is released from axons in a vesicular manner that is tetanus toxin-sensitive. The Ca2+ source for vesicular fusion is provided by ryanodine receptors on axonal Ca2+ stores, controlled by L-type Ca2+ channels that sense depolarization of the internodal axolemma. Genetic ablation of GluN2D and GIuN3A subunits results in greater lability of the compact myelin. Our results support the existence of a novel synapse between the axon and its myelin, suggesting a means by which traversing action potentials can signal the overlying myelin sheath. This may be an important physiological mechanism by which an axon can signal companion glia for metabolic support or adjust properties of its myelin in a dynamic manner. The axo-myelinic synapse may contribute to learning, while its disturbances may play a role in the pathophysiology of central nervous system disorders such as schizophrenia, where subtle abnormalities of myelinated white matter tracts have been shown in the human, or to frank demyelinating disorders such as multiple sclerosis. (C) 2015 Elsevier Inc. All rights reserved.