Institute of Neuronal Cell Biology, Technical University of Munich, Biedersteiner Strasse 29, 80802 Munich, Germany; Graduate School of Systemic Neurosciences (GSN), Ludwig-Maximilian University of Munich, Großhaderner Strasse 2, 82152 Planegg-Martinsried, Germany.
Institute of Neuronal Cell Biology, Technical University of Munich, Biedersteiner Strasse 29, 80802 Munich, Germany.
Curr Biol. 2018 Feb 19;28(4):549-559.e3. doi: 10.1016/j.cub.2018.01.017. Epub 2018 Feb 8.
The length of myelin sheaths affects conduction speed along axons and information propagation. It has recently become clear that myelin may be adaptively modified to modulate circuit function, implying that length remodeling of myelin sheaths should occur. However, direct evidence for such events is lacking. We have investigated how myelination patterns are formed, maintained, and remodeled using long-term imaging and myelin ablation in zebrafish. We demonstrate that length differences between myelin sheaths are established by rapid and variable growth within 3 days after their formation, independently of their time of formation, and even along discontinuously myelinated axons. Afterward, sheaths continue extending at similar rates to compensate for overall animal growth. In consequence, once axon myelination patterns are established, they are maintained over long periods of time. We tested whether mature myelin sheaths can remodel by removing individual sheaths from single axons by targeted ablation. Remarkably, extensive changes in sheath length and number occurred, which frequently restored the original myelination pattern. Our results show that axons can control myelin growth and remodeling, and we provide evidence for a homeostatic control of axon myelination patterns by maintenance and remodeling of myelin sheath length, with implications for circuit development, function, and repair.
髓鞘的长度会影响轴突上的电信号传导速度和信息传递。最近人们发现，髓鞘可能会发生适应性改变来调节回路功能，这意味着髓鞘的长度可能会发生重塑。然而，目前还缺乏此类事件的直接证据。我们利用斑马鱼中的长期成像和髓鞘消融技术，研究了髓鞘的形成、维持和重塑方式。研究结果表明，髓鞘形成后 3 天内，髓鞘会通过快速且多变的生长来建立长度差异，这一过程与髓鞘形成时间无关，甚至可以发生在不连续髓鞘化的轴突上。此后，髓鞘会以相似的速度继续延伸，以补偿动物的整体生长。因此，一旦轴突的髓鞘模式建立，它们就可以长时间维持。为了验证成熟的髓鞘是否可以发生重塑，我们通过靶向消融的方法从单个轴突上去除单个髓鞘。结果令人惊讶，鞘的长度和数量发生了广泛的变化，且经常恢复到原始的髓鞘模式。我们的研究结果表明，轴突可以控制髓鞘的生长和重塑，为维持和重塑髓鞘长度对轴突髓鞘化模式的稳态控制提供了证据，这对回路的发育、功能和修复具有重要意义。
