Adenosine signaling in glia modulates metabolic state-dependent behavior in Drosophila

An animals metabolic state strongly influences its behavior. Hungry animals prioritize food seeking and feeding behaviors, while sated animals suppress these behaviors to engage in other activities. Additionally, neuronal activity and synaptic transmission are among the most energy expensive processes. Yet neurons do not uptake nutrients from the circulation. Instead, glia fulfill this highly evolutionary conserved function. Recent studies have shown that glia can modulate neuronal activity and behavior. However, how different glia subtypes sense metabolic state and modulate neurons and behavior is incompletely understood. Here, we unravel two types of glia-mediated modulation of metabolic state-dependent behavior. In food-deprived flies, astrocyte-like and perineurial glia promote foraging and feeding, respectively, while cortex glia suppress these behaviors. We further show that adenosine and adenosine receptor modulate intracellular calcium levels in these glia subtypes, which ultimately controls behavior. This study reveals a new mechanism how different glia subtypes sense the metabolic state of the animal and modulate its behavior accordingly.