Cross-Modulation of Homeostatic Responses to Temperature, Oxygen and Carbon Dioxide in C. elegans

Different interoceptive systems must be integrated to ensure that multiple homeostatic insults evoke appropriate behavioral and physiological responses. Little is known about how this is achieved. Using C. elegans, we dissect cross-modulation between systems that monitor temperature, O(2) and CO(2). CO(2) is less aversive to animals acclimated to 15°C than those grown at 22°C. This difference requires the AFD neurons, which respond to both temperature and CO(2) changes. CO(2) evokes distinct AFD Ca(2+) responses in animals acclimated at 15°C or 22°C. Mutants defective in synaptic transmission can reprogram AFD CO(2) responses according to temperature experience, suggesting reprogramming occurs cell autonomously. AFD is exquisitely sensitive to CO(2). Surprisingly, gradients of 0.01% CO(2)/second evoke very different Ca(2+) responses from gradients of 0.04% CO(2)/second. Ambient O(2) provides further contextual modulation of CO(2) avoidance. At 21% O(2) tonic signalling from the O(2)-sensing neuron URX inhibits CO(2) avoidance. This inhibition can be graded according to O(2) levels. In a natural wild isolate, a switch from 21% to 19% O(2) is sufficient to convert CO(2) from a neutral to an aversive cue. This sharp tuning is conferred partly by the neuroglobin GLB-5. The modulatory effects of O(2) on CO(2) avoidance involve the RIA interneurons, which are post-synaptic to URX and exhibit CO(2)-evoked Ca(2+) responses. Ambient O(2) and acclimation temperature act combinatorially to modulate CO(2) responsiveness. Our work highlights the integrated architecture of homeostatic responses in C. elegans.