Context-dependent serotonin signaling links dietary quality to foraging decisions.

Animals sense their metabolic needs to guide adaptive behaviors partly through serotonin, a neurotransmitter associated with feeding in many species. Here we investigate the ability of the serotonin system to evaluate and interpret diverse diets by studying long-term foraging behaviors of the nematode C. elegans on bacteria. Behavioral screens on a genome-wide collection of E coli strains identified 22 metabolic mutants that induce behavioral aversion and stress responses in C. elegans. We show that different classes of serotonergic neurons promote aversion to non-preferred E. coli diets and retention on preferred E. coli diets, respectively, through different serotonin receptors. Serotonin is integrated with dopamine and octopamine signals across distributed circuits to direct opposing behavioral responses to preferred and aversive diets. These results reveal interacting neuromodulatory circuits that guide context-dependent evaluation of dietary quality.