A Single Set of Interneurons Drives Opposite Behaviors in C. elegans.

Many chemosensory stimuli evoke innate behavioral responses that can be either appetitive or aversive, depending on an animal's age, prior experience, nutritional status, and environment [1-9]. However, the circuit mechanisms that enable these valence changes are poorly understood. Here, we show that Caenorhabditis elegans can alternate between attractive or aversive responses to carbon dioxide (CO2), depending on its recently experienced CO2 environment. Both responses are mediated by a single pathway of interneurons. The CO2-evoked activity of these interneurons is subject to extreme experience-dependent modulation, enabling them to drive opposite behavioral responses to CO2. Other interneurons in the circuit regulate behavioral sensitivity to CO2 independent of valence. A combinatorial code of neuropeptides acts on the circuit to regulate both valence and sensitivity. Chemosensory valence-encoding interneurons exist across phyla, and valence is typically determined by whether appetitive or aversive interneuron populations are activated. Our results reveal an alternative mechanism of valence determination in which the same interneurons contribute to both attractive and aversive responses through modulation of sensory neuron to interneuron synapses. This circuit design represents a previously unrecognized mechanism for generating rapid changes in innate chemosensory valence.