Norepinephrine regulates calcium signals and fate of oligodendrocyte precursor cells in the mouse cerebral cortex.

Oligodendrocyte precursor cells (OPCs) generate oligodendrocytes, contributing to myelination and myelin repair. OPCs contact axons and respond to neuronal activity, but how the information relayed by the neuronal activity translates into OPC Ca 2+ signals, which in turn influence their fate, remains unknown. We generated transgenic mice for concomitant monitoring of OPCs Ca 2+ signals and cell fate using 2-photon microscopy in the somatosensory cortex of awake-behaving mice. Ca 2+ signals in OPCs mainly occur within processes and confine to Ca 2+ microdomains. A subpopulation of OPCs enhances Ca 2+ transients while mice engaged in exploratory locomotion. We found that OPCs responsive to locomotion preferentially differentiate into oligodendrocytes, and locomotion-non-responsive OPCs divide. Norepinephrine mediates locomotion-evoked Ca 2+ increases in OPCs by activating α1 adrenergic receptors, and chemogenetic activation of OPCs or noradrenergic neurons promotes OPC differentiation. Hence, we uncovered that for fate decisions OPCs integrate Ca 2+ signals, and norepinephrine is a potent regulator of OPC fate.