Mazuir Elisa, Richevaux Louis, Nassar Merie, Robil Noémie, de la Grange Pierre, Lubetzki Catherine, Fricker Desdemona, Sol-Foulon Nathalie
Sorbonne University, Inserm, CNRS, Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, F-75013 Paris, France.
Université de Paris, INCC UMR 8002, CNRS, F-75006 Paris.
Cereb Cortex. 2021 Oct 1;31(11):5024-5041. doi: 10.1093/cercor/bhab139.
Oligodendrocytes form myelin for central nervous system axons and release factors which signal to neurons during myelination. Here, we ask how oligodendroglial factors influence hippocampal GABAergic neuron physiology. In mixed hippocampal cultures, GABAergic neurons fired action potentials (APs) of short duration and received high frequencies of excitatory synaptic events. In purified neuronal cultures without glial cells, GABAergic neuron excitability increased and the frequency of synaptic events decreased. These effects were largely reversed by adding oligodendrocyte conditioned medium (OCM). We compared the transcriptomic signature with the electrophysiological phenotype of single neurons in these three culture conditions. Genes expressed by single pyramidal or GABAergic neurons largely conformed to expected cell-type specific patterns. Multiple genes of GABAergic neurons were significantly downregulated by the transition from mixed cultures containing glial cells to purified neuronal cultures. Levels of these genes were restored by the addition of OCM to purified cultures. Clustering genes with similar changes in expression between different culture conditions revealed processes affected by oligodendroglial factors. Enriched genes are linked to roles in synapse assembly, AP generation, and transmembrane ion transport, including of zinc. These results provide new insight into the molecular targets by which oligodendrocytes influence neuron excitability and synaptic function.
少突胶质细胞为中枢神经系统轴突形成髓鞘，并在髓鞘形成过程中释放向神经元发出信号的因子。在此，我们探讨少突胶质细胞因子如何影响海马体GABA能神经元的生理学特性。在混合海马体培养物中，GABA能神经元产生持续时间短的动作电位（APs），并接收高频兴奋性突触事件。在没有胶质细胞的纯化神经元培养物中，GABA能神经元的兴奋性增加，突触事件的频率降低。添加少突胶质细胞条件培养基（OCM）可在很大程度上逆转这些效应。我们比较了这三种培养条件下单神经元的转录组特征与电生理表型。单个锥体神经元或GABA能神经元表达的基因在很大程度上符合预期的细胞类型特异性模式。从含有胶质细胞的混合培养物转变为纯化神经元培养物后，GABA能神经元的多个基因显著下调。向纯化培养物中添加OCM可恢复这些基因的水平。对不同培养条件下表达变化相似的基因进行聚类，揭示了受少突胶质细胞因子影响的过程。富集的基因与突触组装、AP产生和跨膜离子转运（包括锌的转运）中的作用相关。这些结果为少突胶质细胞影响神经元兴奋性和突触功能的分子靶点提供了新的见解。
