Abstract

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 (CO2). C. elegans exhibits highly flexible responses to CO2: well-fed animals are repelled by CO2, while both starved animals and well-fed animals raised under high CO2 conditions are attracted to CO2. Here, we show that CO2 attraction in animals raised at high CO2 requires a cGMP signaling pathway that involves the cGMP-dependent protein kinase EGL-4. This pathway does not regulate CO2 response in starved animals, indicating that the role of EGL-4 in mediating CO2 attraction depends on satiety state. Cultivation under high CO2 conditions leads to increased cGMP levels in the CO2-detecting BAG neurons, consistent with a specific requirement for EGL-4 in high-CO2-cultivated animals. We also show that EGL-4 regulates CO2 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.