Dopamine-induced astrocytic Ca2+ signaling in mPFC is mediated by MAO-B in young mice, but by dopamine receptors in adult mice

Abstract

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 D₁-like or D₂-like dopamine receptors, respectively. In contrast, it has been elusive how astrocytes respond to DA via Ca²⁺ signaling and regulate synaptic transmission and reward systems. Previous studies suggest various molecular targets such as MAO-B, D₁R, or D₁R-D₂R heteromer to modulate astrocytic Ca²⁺ signaling. However, which molecular target is utilized under what physiological condition remains unclear. Here, we show that DA-induced astrocytic Ca²⁺ 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 Ca²⁺ response in the adult period was decreased by either D₁R or D₂R blockers, which are primarily known for cyclic AMP signaling (G_s and G_i pathway, respectively), suggesting that this Ca²⁺ response might be mediated through G_q pathway by D₁R-D₂R heterodimer. Moreover, DAR-mediated Ca²⁺ 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 Ca²⁺ signaling: MAO-B in young mice and DAR in adult mice.

Keywords: Astrocyte; Ca2+ response; Development; Dopamine; Dopamine receptors; MAO-B; mPFC.