Li Jiaxing, Miramontes Tania G, Czopka Tim, Monk Kelly R
Vollum Institute, Oregon Health & Science University, Portland, OR, USA.
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
Nat Neurosci. 2024 Feb;27(2):219-231. doi: 10.1038/s41593-023-01553-8. Epub 2024 Jan 12.
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 Ca 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 Ca 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 Ca signaling.
在神经系统中，已知仅存在一种神经元 - 神经胶质突触：即神经元与少突胶质前体细胞（OPC）之间的突触，然而其组成、组装、下游信号传导及体内功能仍大多不明。在此，我们利用斑马鱼脊髓的体内显微镜技术来解决这些问题，并在OPC中鉴定出突触后分子PSD - 95和gephyrin。OPC中含有这些分子的斑点在早期发育过程中增加，而在OPC分化时减少。这些斑点高度动态，且经常在“热点”处组装。OPC中的gephyrin热点和突触相关的钙活性可预测分化的少突胶质细胞中髓鞘形成的一个子集的位置。进一步分析表明，自发突触释放是OPC钙活性所必需的，而诱发突触释放仅在早期发育中起作用。最后，突触基因dlg4a/dlg4b、gphnb和nlgn3b的破坏会损害OPC分化和髓鞘形成。我们共同提出，神经元 - OPC突触是动态组装的，并且可以通过钙信号传导预先确定髓鞘形成模式。
