Tonic signaling from O₂ sensors sets neural circuit activity and behavioral state

Tonic receptors convey stimulus duration and intensity and are implicated in homeostatic control. However, how tonic homeostatic signals are generated and how they reconfigure neural circuits and modify animal behavior is poorly understood. Here we show that Caenorhabditis elegans O(2)-sensing neurons are tonic receptors that continuously signal ambient [O(2)] to set the animal's behavioral state. Sustained signaling relied on a Ca(2+) relay involving L-type voltage-gated Ca(2+) channels, the ryanodine and the inositol-1,4,5-trisphosphate receptors. Tonic activity evoked continuous neuropeptide release, which helps elicit the enduring behavioral state associated with high [O(2)]. Sustained O(2) receptor signaling was propagated to downstream neural circuits, including the hub interneuron RMG. O(2) receptors evoked similar locomotory states at particular O(2) concentrations, regardless of previous d[O(2)]/dt. However, a phasic component of the URX receptors' response to high d[O(2)]/dt, as well as tonic-to-phasic transformations in downstream interneurons, enabled transient reorientation movements shaped by d[O(2)]/dt. Our results highlight how tonic homeostatic signals can generate both transient and enduring behavioral change.