@article {70177, title = {A pair of interneurons that assign positive valence to sweet sensation in Drosophila}, journal = {Curr Bill}, year = {2026}, month = {2026 Jan 29}, 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 circuits that transform taste into motivationally relevant signals remain poorly defined in any model system. In Drosophila melanogaster, substantial progress has been made in mapping the sensorimotor pathways encoding intrinsic valence for feeding and the architecture of the dopaminergic reinforcement system. However, where and how "effective" (i.e., real-time) valence is first imposed on a taste has long been a mystery. Here, we identified a pair of subesophageal zone interneurons in Drosophila, termed Fox, that impart reinforcing positive valence to sweet taste and convey this signal to the mushroom body, the fly{\textquoteright}s associative learning center. We show that Fox neuron activity is necessary and sufficient to drive appetitive behaviors and can override a tastant{\textquoteright}s intrinsic neutral or aversive valence without impairing taste quality discrimination. Furthermore, Fox neurons relay the positive valence to specific dopaminergic neurons that mediate appetitive memory formation. Our findings reveal a circuit mechanism through which effective valence is bestowed upon sweet sensation and transformed into a reinforcing signal that supports learned sugar responses. The Fox neurons form 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.

}, doi = {10.1016/j.cub.2025.12.058}, url = {https://doi.org/10.1016/j.cub.2025.12.058}, author = {Christie, Kevin William and Dadyala, Tarandeep Singh and Sinakevitch, Irina Troufakina and Chung, Phuong and Ito, Masayoshi and Shao, Lisha} }