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

Abstract

An animals response to chemosensory cues depends on the animals 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.