Hunger and thirst are ancient homeostatic drives for food and water consumption. Although molecular and neural mechanisms underlying these drives are currently being uncovered, less is known about how hunger and thirst interact. Here, we use molecular genetic, behavioral, and anatomical studies in Drosophila to identify four neurons that modulate food and water consumption. Activation of these neurons promotes sugar consumption and restricts water consumption, whereas inactivation promotes water consumption and restricts sugar consumption. By calcium imaging studies, we show that these neurons are directly regulated by a hormone signal of nutrient levels and by osmolality. Finally, we identify a hormone receptor and an osmolality-sensitive ion channel that underlie this regulation. Thus, a small population of neurons senses internal signals of nutrient and water availability to balance sugar and water consumption. Our results suggest an elegant mechanism by which interoceptive neurons oppositely regulate homeostatic drives to eat and drink.

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In animals, nervous systems regulate the ingestion of food and water in a manner that reflects internal metabolic need. While the coordination of these two ingestive behaviors is essential for homeostasis, it has been unclear how internal signals of hunger and thirst interact to effectively coordinate food and water ingestion. In the last year, work in insects and mammals has begun to elucidate some of these interactions. As reviewed here, these studies have identified novel molecular and neural mechanisms that coordinate the regulation of food and water ingestion behaviors. These mechanisms include peptide signals that modulate neural circuits for both thirst and hunger, neurons that regulate both food and water ingestion, and neurons that integrate sensory information about both food and water in the external world. These studies argue that a deeper understanding of hunger and thirst will require closer examination of how these two biological drives interact.

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