Abstract
Spiking immature oligodendrocytes (OLs), referred to as spiking OLs, express voltage-activated Na+ channels (Nav) and K+ (Kv) channels, endowing a subpopulation of OLs with the ability to generate Nav-driven spikes. In this study, we investigate the molecular profile of spiking OLs, using single-cell transcriptomics paired with whole-cell patch-clamp recordings. SCN2A, which encodes the channel Nav1.2, is specifically expressed in spiking OLs in the brainstem and cerebellum, both in mice and in Olive baboons. Spiking OLs express lineage markers of OL progenitor cells (OPCs) and pre-myelinating OLs, indicating they belong to a transitional stage during differentiation. Deletion of SCN2A reduces the Nav current-expressing OL population and eliminates spiking OLs, indicating that SCN2A is essential for spiking in OLs. Deletion of SCN2A does not impact global OL proliferation but disrupts maturation of a subpopulation of OLs, suggesting that Nav1.2 is involved in heterogeneity in OL lineage cells and their development.