Most heritable behavioral traits have a complex genetic basis, but few multigenic traits are understood at a molecular level. Here we show that the C. elegans strains N2 and CB4856 have opposite behavioral responses to simultaneous changes in environmental O2 and CO2. We identify two quantitative trait loci (QTL) that affect this trait, and map each QTL to a single-gene polymorphism. One gene, npr-1, encodes a previously described neuropeptide receptor whose high activity in N2 promotes CO2 avoidance. The second gene, glb-5, encodes a neuronal globin domain protein whose high activity in CB4856 modifies behavioral responses to O2 and combined O2/CO2 stimuli. glb-5 acts in O2–sensing neurons to increase O2-evoked calcium signals, implicating globins in sensory signaling. An analysis of wild C. elegans strains indicates that the N2 alleles of npr-1 and glb-5 arose recently in the same strain background, possibly as an adaptation to laboratory conditions.

SUMMARY Pheromone responses are highly context-dependent. For example, the C. elegans pheromone ascaroside C9 (ascr#3) is repulsive to wild-type hermaphrodites, attractive to wild-type males, and usually neutral to “social” hermaphrodites with reduced activity of the npr-1 neuropeptide receptor gene. We show here that these distinct behavioral responses arise from overlapping push-pull circuits driven by two classes of pheromone-sensing neurons. The ADL sensory neurons detect C9, and in wild-type hermaphrodites, drive C9 repulsion through their chemical synapses. In npr-1 mutant hermaphrodites, C9 repulsion is reduced by the recruitment of a gap junction circuit that antagonizes ADL chemical synapses. In males, ADL sensory responses are diminished; in addition, a second pheromone-sensing neuron, ASK, antagonizes C9 repulsion. The additive effects of these antagonistic circuit elements generate attractive, repulsive or neutral pheromone responses. Neuronal modulation by circuit state and sex, and flexibility in synaptic output pathways, may permit small circuits to maximize their adaptive behavioral outputs.

Soma-Targeted Imaging of Neural Circuits by Ribosome TetheringHighlights d Ribosome tethering restricts fluorescent proteins to the cell soma d A ribo-nanobody mouse boosts the fluorescence of existing GFP reporters d Ribo-GCaMP reduces fluorescence cross-contamination during 2P calcium imaging d Ribo-GCaMP enables whole-brain imaging of somatic calcium dynamics in the worm Authors