Neuronal activity biases axon selection for myelination in vivo.

Neuronal activity biases axon selection for myelination in vivo.
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神经元活动会影响体内髓鞘形成的轴突选择。

DOI:
10.1038/nn.3992
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发表时间:
2015-05
影响因子:
25
通讯作者:
Appel, Bruce
Appel, Bruce
中科院分区:
医学1区
文献类型:
--
作者:
Hines, Jacob H.;Ravanelli, Andrew M.;Schwindt, Rani;Scott, Ethan K.;Appel, Bruce

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脊椎动物神经发育的一个基本特征是轴突被髓鞘包裹,髓鞘是一种由少突胶质细胞形成的绝缘膜。并非所有的轴突都有髓鞘形成,但指导特定轴突髓鞘形成的机制尚不清楚。使用斑马鱼,我们发现活动依赖性分泌稳定髓鞘形成的选择轴突。当vamp2依赖的胞吐作用在单个轴突中被沉默时,少突胶质细胞优先包裹邻近的轴突。在沉默轴突上形成的新生鞘长度较短,但当邻近轴突的活动也受到抑制时,鞘生长的抑制得到缓解。使用体内延时显微镜,我们发现在正常发育过程中,只有25%启动轴突包裹的少突胶质细胞过程是稳定的,并且这种启动不需要活动。相反,包裹沉默轴突的少突胶质突更频繁地收缩。我们提出,轴突选择髓鞘形成的结果是过度和不加区分地开始包裹,然后细化,这是由轴突的活动依赖性分泌偏倚。
An essential feature of vertebrate neural development is ensheathment of axons with myelin, an insulating membrane formed by oligodendrocytes. Not all axons are myelinated, but mechanisms directing myelination of specific axons are unknown. Using zebrafish we show that activity-dependent secretion stabilizes myelin sheath formation on select axons. When VAMP2-dependent exocytosis is silenced in single axons, oligodendrocytes preferentially ensheath neighboring axons. Nascent sheaths formed on silenced axons are shorter in length, but when activity of neighboring axons is also suppressed, inhibition of sheath growth is relieved. Using in vivo time-lapse microscopy, we show that only 25% of oligodendrocyte processes that initiate axon wrapping are stabilized during normal development, and that initiation does not require activity. Instead, oligodendrocyte processes wrapping silenced axons are retracted more frequently. We propose that axon selection for myelination results from excessive and indiscriminate initiation of wrapping followed by refinement that is biased by activity-dependent secretion from axons.
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