Norepinephrine enhances oligodendrocyte precursor cell calcium dynamics in the cerebral cortex during arousal

Oligodendrocytes are generated from a widely distributed population of progenitors that express neurotransmitter receptors, but the mechanisms that alter activity of these oligodendrocyte precursor cells (OPCs) in vivo have not been determined. We generated a novel line of transgenic mice to express membrane-anchored GCaMP6s in OPCs and used longitudinal two-photon microscopy to monitor their Ca2+ changes in the cerebral cortex of awake mice. OPCs exhibited high rates of spontaneous activity, consisting of focal, transient Ca2+ increases within their highly ramified processes. Unexpectedly, these events occurred independent of excitatory neuron activity, but were inhibited by anesthesia, sedative agents, and antagonists of noradrenergic signaling. These norepinephrine enhanced Ca2+ dynamics rapidly declined as with differentiation. Selective knockout of 1A adrenergic receptors in OPCs suppressed both spontaneous and locomotion-induced Ca2+ increases, indicating that OPCs are directly modulated by norepinephrine in vivo, providing a means to alter their dynamics and lineage progression during distinct brain states.