Independent, Reciprocal Neuromodulatory Control of Sweet and Bitter Taste Sensitivity during Starvation in Drosophila

An organism’s behavioral decisions often depend upon the relative strength of appetitive and aversive sensory stimuli, the relative sensitivity to which can be modified by internal states like hunger. However, whether sensitivity to such opposing influences is modulated in a unidirectional or bidirectional manner is not clear. Starved flies exhibit increased sugar and decreased bitter sensitivity. It is widely believed that only sugar sensitivity changes, and that this masks bitter sensitivity. Here we use gene- and circuit-level manipulations to show that sweet and bitter sensitivity are independently and reciprocally regulated by starvation in Drosophila. We identify orthogonal neuromodulatory cascades that oppositely control peripheral taste sensitivity for each modality. Moreover, these pathways are recruited at increasing hunger levels, such that low-risk changes (higher sugar sensitivity) precede high-risk changes (lower sensitivity to potentially toxic resources). In this way, state-intensity-dependent, reciprocal regulation of appetitive and aversive peripheral gustatory sensitivity permits flexible, adaptive feeding decisions. •Sugar and bitter sensitivity change independently and oppositely in starved flies•Parallel neuromodulatory pathways reciprocally control peripheral taste sensitivity•Sweet and bitter sensitivity change at progressively longer starvation times•Low- versus high-risk changes in feeding behavior occur with increasing energy deficit Sweet and bitter taste sensitivity are reciprocally regulated during starvation in Drosophila. This regulation occurs via parallel neuromodulatory pathways that oppositely control peripheral taste sensitivity. These changes occur at different levels of energy deficit. This state-dependent modulation permits adaptive feeding decisions.