美国俄勒冈健康与科学大学Kelly R. Monk等研究人员合作发现，斑马鱼少突胶质前体细胞中的突触输入和Ca2+活性有助于髓鞘形成。2024年1月12日，国际知名学术期刊《自然—神经科学》在线发表了这一成果。

研究人员表示，在神经系统中，已知只存在一种神经元-神经胶质细胞突触：即神经元和少突胶质细胞前体细胞（OPC）之间的突触，但它们的组成、装配、下游信号传导和体内功能在很大程度上仍不清楚。

研究人员利用斑马鱼脊髓的活体显微镜解决了这些问题，并在OPC中鉴定出突触后分子PSD-95和gephyrin。OPC中含有这些分子的点状突触在早期发育过程中增加，在OPC分化过程中减少。这些点状突触具有高度动态性，经常在“热点”处聚集。OPC中的gephyrin热点和突触相关Ca2+活性预测了分化的少突胶质细胞中形成髓鞘的位置。

进一步的分析表明，自发的突触释放与OPC Ca2+活性密不可分，而诱发的突触释放只在发育早期起作用。最后，突触基因dlg4a/dlg4b、gphnb和nlgn3b的破坏会损害OPC的分化和髓鞘化。综上所述，研究人员认为神经元-OPC突触是动态组装的，可以通过Ca2+信号预先决定髓鞘化模式。

附：英文原文

Title: Synaptic input and Ca2+ activity in zebrafish oligodendrocyte precursor cells contribute to myelin sheath formation

Author: Li, Jiaxing, Miramontes, Tania G., Czopka, Tim, Monk, Kelly R.

Issue&Volume: 2024-01-12

Abstract: In the nervous system, only one type of neuron–glial synapse is known to exist: that between neurons and oligodendrocyte precursor cells (OPCs), yet their composition, assembly, downstream signaling and in vivo functions remain largely unclear. Here, we address these questions using in vivo microscopy in zebrafish spinal cord and identify postsynaptic molecules PSD-95 and gephyrin in OPCs. The puncta containing these molecules in OPCs increase during early development and decrease upon OPC differentiation. These puncta are highly dynamic and frequently assemble at 'hotspots'. Gephyrin hotspots and synapse-associated Ca2+ activity in OPCs predict where a subset of myelin sheaths forms in differentiated oligodendrocytes. Further analyses reveal that spontaneous synaptic release is integral to OPC Ca2+ activity, while evoked synaptic release contributes only in early development. Finally, disruption of the synaptic genes dlg4a/dlg4b, gphnb and nlgn3b impairs OPC differentiation and myelination. Together, we propose that neuron–OPC synapses are dynamically assembled and can predetermine myelination patterns through Ca2+ signaling.

DOI: 10.1038/s41593-023-01553-8

Source: https://www.nature.com/articles/s41593-023-01553-8

期刊信息

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771

官方网址：https://www.nature.com/neuro

投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex