cGMP signaling regulates context-dependent sensory valence in C. elegans

An animal’s response to chemosensory cues depends on the animal’s prior experience, internal state, or life stage. However, the molecular mechanisms that regulate sensory valence ( i.e., whether a chemosensory cue is attractive or repulsive) remain poorly understood. We investigated the mechanisms that specify sensory valence using the responses of the free-living nematode Caenorhabditis elegans to carbon dioxide (CO ₂ ). C. elegans exhibits highly flexible responses to CO ₂ : well-fed animals are repelled by CO ₂ , while both starved animals and well-fed animals raised under high CO ₂ conditions are attracted to CO ₂ . Here, we show that CO ₂ attraction in animals raised at high CO ₂ requires a cGMP signaling pathway that involves the cGMP-dependent protein kinase EGL-4. This pathway does not regulate CO ₂ response in starved animals, indicating that the role of EGL-4 in mediating CO ₂ attraction depends on satiety state. Cultivation under high CO ₂ conditions leads to increased cGMP levels in the CO ₂ -detecting BAG neurons, consistent with a specific requirement for EGL-4 in high-CO ₂ -cultivated animals. We also show that EGL-4 regulates CO ₂ valence by altering neuropeptide expression in BAG. Our results indicate that sensory valence is established in a context-dependent manner at the level of the primary sensory neuron.