Feeding state sculpts a circuit for sensory valence in Caenorhabditis elegans

Hunger affects the behavioral choices of all animals, and many chemosensory stimuli can be either attractive or repulsive depending on an animal's hunger state. Although hunger-induced behavioral changes are well documented, the molecular and cellular mechanisms by which hunger modulates neural circuit function to generate changes in chemosensory valence are poorly understood. Here, we use the CO₂ response of the free-living nematode Caenorhabditis elegans to elucidate how hunger alters valence. We show that CO₂ response valence shifts from aversion to attraction during starvation, a change that is mediated by two pairs of interneurons in the CO₂ circuit, AIY and RIG. The transition from aversion to attraction is regulated by biogenic amine signaling. Dopamine promotes CO₂ repulsion in well-fed animals, whereas octopamine promotes CO₂ attraction in starved animals. Biogenic amines also regulate the temporal dynamics of the shift from aversion to attraction such that animals lacking octopamine show a delayed shift to attraction. Biogenic amine signaling regulates CO₂ response valence by modulating the CO₂-evoked activity of AIY and RIG. Our results illuminate a new role for biogenic amine signaling in regulating chemosensory valence as a function of hunger state.