From perception to valence: a pair of interneurons that assign positive valence to sweet sensation in Drosophila

Abstract

Assigning valence--appeal or aversion--to gustatory stimuli and relaying it to higher-order brain regions to guide flexible behaviors is crucial to survival. Yet the neural circuit that transforms gustatory input into motivationally relevant signals remains poorly defined in any model system. In Drosophila melanogaster, substantial progress has been made in mapping the sensorimotor pathway for feeding and the architecture of the dopaminergic reinforcement system. However, where and how valence is first assigned to a taste has long been a mystery. Here, we identified a pair of subesophageal zone interneurons in Drosophila, termed fox, that impart positive valence to sweet taste and convey this signal to the mushroom body, the flys associative learning center. We show that fox neuron activity is necessary and sufficient to drive appetitive behaviors and can override a tastants intrinsic valence without impairing taste quality discrimination. Furthermore, fox neurons transmit the positive valence to specific dopaminergic neurons that mediate appetitive memory formation. Our findings reveal a circuit mechanism that transforms sweet sensation into a reinforcing signal to support learned sugar responses. The fox neurons exhibit a convergent-divergent "hourglass" circuit motif, acting as a bottleneck for valence assignment and distributing motivational signals to higher-order centers. This architecture confers both robustness and flexibility in reward processing--an organizational principle that may generalize across species.