Oligodendroglial excitability mediated by glutamatergic inputs and Nav1.2 activation

Oligodendrocyte (OL) maturation and axon-glial communication are required for proper myelination in the developing brain. However, physiological properties of OLs remain largely uncharacterized in different brain regions. The roles of oligodendroglial voltage-activated Na+ channels (Na-v) and electrical excitability in relation to maturation to the myelinating stage are controversial, although oligodendroglial excitability is potentially important for promoting axon myelination. Here we show spiking properties of OLs and their role in axon-glial communication in the auditory brainstem. A subpopulation of pre-myelinating OLs (pre-OLs) can generate Na(v)1.2-driven action potentials throughout postnatal development to early adulthood. In addition, excitable pre-OLs receive glutamatergic inputs from neighboring neurons that trigger pre-OL spikes. Knockdown of Na(v)1.2 channels in pre-OLs alters their morphology, reduces axon-OL interactions and impairs myelination. Our results suggest that Na(v)1.2-driven spiking of pre-OLs is an integral component of axon-glial communication and is required for the function and maturation of OLs to promote myelination.