Myelination of axons by oligodendrocytes enables fast saltatory conduction. Oligodendrocytes are responsive to neuronal activity, which has been shown to induce changes to myelin sheaths, potentially to optimize conduction and neural circuit function. However, the cellular bases of activity-regulated myelination in vivo are unclear, partly due to the difficulty of analyzing individual myelinated axons over time. Activity-regulated myelination occurs in specific neuronal subtypes and can be mediated by synaptic vesicle fusion, but several questions remain: it is unclear whether vesicular fusion occurs stochastically along axons or in discrete hotspots during myelination and whether vesicular fusion regulates myelin targeting, formation, and/or growth. It is also unclear why some neurons, but not others, exhibit activity-regulated myelination. Here, we imaged synaptic vesicle fusion in individual neurons in living zebrafish and documented robust vesicular fusion along axons during myelination. Surprisingly, we found that axonal vesicular fusion increased upon and required myelination. We found that axonal vesicular fusion was enriched in hotspots, namely the heminodal non-myelinated domains into which sheaths grew. Blocking vesicular fusion reduced the stable formation and growth of myelin sheaths, and chemogenetically stimulating neuronal activity promoted sheath growth. Finally, we observed high levels of axonal vesicular fusion only in neuronal subtypes that exhibit activity-regulated myelination. Our results identify a novel “feedforward” mechanism whereby the process of myelination promotes the neuronal activity-regulated signal, vesicular fusion that, in turn, consolidates sheath growth along specific axons selected for myelination.

少突胶质细胞对轴突的髓鞘化能够实现快速跳跃传导。少突胶质细胞对神经元活动有反应，这已被证明可以诱导髓鞘的变化，从而可能优化传导和神经回路功能。然而，体内活性调节髓鞘形成的细胞基础尚不清楚，部分原因是随着时间的推移分析单个有髓鞘轴突的困难。活性调节的髓鞘形成发生在特定的神经元亚型中，并且可以通过突触小泡融合介导，但仍然存在几个问题：目前尚不清楚囊泡融合是沿着轴突随机发生还是在髓鞘形成过程中的离散热点中发生，以及囊泡融合是否调节髓磷脂的靶向、形成和形成。 /或成长。还不清楚为什么一些神经元而不是其他神经元表现出活动调节的髓鞘形成。在这里，我们对活体斑马鱼单个神经元的突触小泡融合进行了成像，并记录了髓鞘形成过程中沿着轴突的强小泡融合。令人惊讶的是，我们发现轴突囊泡融合在髓鞘形成时增加并且需要髓鞘形成。我们发现轴突囊泡融合在热点处富集，即鞘生长的半结节非髓鞘区域。阻断囊泡融合会降低髓鞘的稳定形成和生长，而化学遗传学刺激神经元活动会促进髓鞘生长。最后，我们仅在表现出活性调节髓鞘形成的神经元亚型中观察到高水平的轴突囊泡融合。我们的结果确定了一种新的“前馈”机制，髓鞘形成过程促进神经元活动调节信号，即囊泡融合，进而巩固沿着选定用于髓鞘形成的特定轴突的鞘生长。