Four GABAergic Interneurons Impose Feeding Restraint in Drosophila

•Four GABAergic interneurons are required to inhibit ingestive behaviors•Neural inactivation causes consumption of all compounds in starved and fed states•These neurons do not respond to gustatory cues or changes in physiological state•These neurons establish a central feeding threshold essential to gate feeding

SummaryFeeding is dynamically regulated by the palatability of the food source and the physiological needs of the animal. How consumption is controlled by external sensory cues and internal metabolic state remains under intense investigation. Here, we identify four GABAergic interneurons in the Drosophila brain that establish a central feeding threshold which is required to inhibit consumption. Inactivation of these cells results in indiscriminate and excessive intake of all compounds, independent of taste quality or nutritional state. Conversely, acute activation of these neurons suppresses consumption of water and nutrients. The output from these neurons is required to gate activity in motor neurons that control meal initiation and consumption. Thus, our study reveals a layer of inhibitory control in feeding circuits that is required to suppress a latent state of unrestricted and nonselective consumption.