Abstract
<jats:p> 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 ( <jats:italic>i.e.,</jats:italic> 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 <jats:italic>Caenorhabditis elegans</jats:italic> to carbon dioxide (CO <jats:sub>2</jats:sub> ). <jats:italic>C. elegans</jats:italic> exhibits highly flexible responses to CO <jats:sub>2</jats:sub> : well-fed animals are repelled by CO <jats:sub>2</jats:sub> , while both starved animals and well-fed animals raised under high CO <jats:sub>2</jats:sub> conditions are attracted to CO <jats:sub>2</jats:sub> . Here, we show that CO <jats:sub>2</jats:sub> attraction in animals raised at high CO <jats:sub>2</jats:sub> requires a cGMP signaling pathway that involves the cGMP-dependent protein kinase EGL-4. This pathway does not regulate CO <jats:sub>2</jats:sub> response in starved animals, indicating that the role of EGL-4 in mediating CO <jats:sub>2</jats:sub> attraction depends on satiety state. Cultivation under high CO <jats:sub>2</jats:sub> conditions leads to increased cGMP levels in the CO <jats:sub>2</jats:sub> -detecting BAG neurons, consistent with a specific requirement for EGL-4 in high-CO <jats:sub>2</jats:sub> -cultivated animals. We also show that EGL-4 regulates CO <jats:sub>2</jats:sub> 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. </jats:p>