Dopamine-induced astrocytic Ca(2+) signaling in mPFC is mediated by MAO-B in young mice, but by dopamine receptors in adult mice

Dopamine (DA) plays a vital role in brain physiology and pathology such as learning and memory, motor control, neurological diseases, and psychiatric diseases. In neurons, it has been well established that DA increases or decreases intracellular cyclic AMP (cAMP) through D(1)-like or D(2)-like dopamine receptors, respectively. In contrast, it has been elusive how astrocytes respond to DA via Ca(2+) signaling and regulate synaptic transmission and reward systems. Previous studies suggest various molecular targets such as MAO-B, D(1)R, or D(1)R–D(2)R heteromer to modulate astrocytic Ca(2+) signaling. However, which molecular target is utilized under what physiological condition remains unclear. Here, we show that DA-induced astrocytic Ca(2+) signaling pathway switches during development: MAO-B is the major player at a young age (5–6 weeks), whereas DA receptors (DARs) are responsible for the adult period (8–12 weeks). DA-mediated Ca(2+) response in the adult period was decreased by either D(1)R or D(2)R blockers, which are primarily known for cyclic AMP signaling (G(s) and G(i) pathway, respectively), suggesting that this Ca(2+) response might be mediated through G(q) pathway by D(1)R–D(2)R heterodimer. Moreover, DAR-mediated Ca(2+) response was not blocked by TTX, implying that this response is not a secondary response caused by neuronal activation. Our study proposes an age-specific molecular target of DA-induced astrocytic Ca(2+) signaling: MAO-B in young mice and DAR in adult mice.