Adrenergic signaling gates astrocyte responsiveness to neurotransmitters and control of neuronal activity

How astrocytes regulate neuronal circuits is a fundamental, unsolved question in neurobiology. Nevertheless, few studies have explored the rules that govern when astrocytes respond to different neurotransmitters in vivo and how they affect downstream circuit modulation. Here, we report an unexpected mechanism in Drosophila 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. Finally, we demonstrate that this gating mechanism is conserved in mammalian astrocytes, arguing it is an ancient feature of astrocyte circuit function. Our work establishes a new mechanism by which astrocytes dynamically respond to and modulate neuronal activity in different brain regions and in different behavioral states.