Myelination induces axonal hotspots of synaptic vesicle fusion that promote sheath growth.
Myelination induces axonal hotspots of synaptic vesicle fusion that promote sheath growth.
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DOI：
10.1016/j.cub.2021.06.036
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发表时间：
2021-09-13
期刊：
影响因子：
--
通讯作者：
Lyons DA
中科院分区：
文献类型：
--
作者：
Almeida RG;Williamson JM;Madden ME;Early JJ;Voas MG;Talbot WS;Bianco IH;Lyons DA
由少突胶质细胞形成的轴突髓鞘使快速跃式传导成为可能。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，潜在地优化传导和神经回路功能。然而，体内活动调节的髓鞘形成的细胞基础尚不清楚，部分原因是难以随时间分析单个髓鞘轴突。活动调节的髓鞘形成发生在特定的神经元亚型中，可通过突触囊泡融合介导，但仍存在几个问题：目前尚不清楚在髓鞘形成过程中，囊泡融合是沿着轴突随机发生还是在离散的热点发生，以及囊泡融合是否调节髓鞘靶向、形成和/或生长。目前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，我们对活斑马鱼单个神经元的突触囊泡融合进行了成像，并记录了髓鞘形成过程中沿轴突的强大囊泡融合。令人惊讶的是，我们发现轴突囊泡融合在髓鞘形成后增加并需要髓鞘形成。我们发现轴突囊泡融合富集在热点区域，即鞘生长的半节无髓鞘区域。阻断囊泡融合降低了髓鞘的稳定形成和生长，化学上刺激神经元活动促进了鞘的生长。最后，我们观察到高水平的轴突囊泡融合仅在表现出活动调节的髓鞘形成的神经元亚型中。我们的研究结果确定了一种新的“前馈”机制，即髓鞘形成过程促进神经元活动调节信号，即囊泡融合，进而巩固鞘生长沿着特定轴突选择髓鞘形成。斑马鱼脊髓轴突髓鞘形成过程中的突触囊泡融合神经元亚型特异性差异髓鞘形成的发生与轴突囊泡融合活动相一致并促进轴突囊泡融合，而囊泡融合促进鞘的稳定性和生长Almeida等人表明，在发育中的斑马鱼脊髓中，沿轴突的突触囊泡融合与某些神经元亚型的突触前终末一样频繁。在这些神经元中，髓鞘形成促进轴突囊泡融合，进而巩固鞘的形成和生长。
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. Live-imaged synaptic vesicular fusion during myelination of zebrafish spinal axons Neuron-subtype specific differences in axonal vesicular fusion Onset of myelination coincides with and promotes axonal vesicular fusion Activity and vesicular fusion promote sheath stability and growth Almeida et al. show that fusion of synaptic vesicles along axons in the developing zebrafish spinal cord is as frequent as at presynaptic terminals in some neuronal subtypes. In these neurons, axonal vesicular fusion is promoted by myelination and in turn consolidates sheath formation and growth.
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影响因子：
25
作者：
Hughes EG;Orthmann-Murphy JL;Langseth AJ;Bergles DE
通讯作者：
Bergles DE
影响因子：
7.8
作者：
Bekku, Yoko;Salzer, James L.
通讯作者：
Salzer, James L.
影响因子：
2.5
作者：
Gahtan, E;O'Malley, DM
通讯作者：
O'Malley, DM
DOI：
10.1016/j.cub.2018.02.068
发表时间：
2018-04-23
期刊：
Current biology : CB
影响因子：
--
作者：
Almeida RG;Pan S;Cole KLH;Williamson JM;Early JJ;Czopka T;Klingseisen A;Chan JR;Lyons DA
通讯作者：
Lyons DA
影响因子：
25
作者：
Baraban M;Koudelka S;Lyons DA
通讯作者：
Lyons DA