GPCR signaling gates astrocyte responsiveness to neurotransmitters and control of neuronal activity.

How astrocytes regulate neuronal circuits is a fundamental question in neurobiology. Specifically, how astrocytes respond to different neurotransmitters in vivo and how they affect downstream circuit modulation are questions that remain to be fully elucidated. Here, we report a mechanism in by which G protein-coupled adrenergic signaling in astrocytes can control-or "gate"-their ability to respond to other neurotransmitters. Further, we show that manipulating this pathway potently regulates neuronal circuit activity and animal behavior. This gating mechanism is conserved in cultured primary mammalian astrocytes, suggesting that it might be an ancient feature of astrocyte circuit function. Our work establishes a mechanism by which astrocytes dynamically respond to and modulate neuronal activity in different brain regions and in different behavioral states.