To maintain homeostasis of the body or avoid dangerous environments, all animals must continuously monitor key sensory information such as oxygen levels. Tonic sensory receptors can perceive such constant information but are not well understood. How do sensors sustain responses to external signals for long periods of time, and how do they reconfigure neural circuits to generate a prolonged change in behaviour?Caenorhabditis elegans provides a unique opportunity to explore homeostatic sensing and tonic signalling in the living organism. It regulates oxygen homeostasis by mounting sophisticated behavioural responses to ambient O2, preferring concentrations substantially below atmospheric levels. Using calcium imaging, behavioural assays and optogenetic stimulation, we studied the mechanisms underlying avoidance of high [O2]. We found that four O2-sensing neurons continuously respond to ambient oxygen. Tonic signalling in these neurons is sustained by a ‘calcium relay’ that consists of cGMP-gated channels, voltage-gated Ca2+ channels, as well as the ryanodine and IP3 receptor channels which release calcium from intracellular stores (Busch et al., 2012). Tonic activity of these neurons is necessary and sufficient to set the behavioural state according to ambient [O2] for many minutes and even hours. Tonic signalling propagates to downstream neural circuits, including the “hub interneuron” RMG, which is thought to integrate inputs from diverse sensory neurons and is required to mediate O2 responses.The tuning of oxygen responses shows plasticity depending on experience, context, or genetic background. Experience-dependent plasticity forms directly in the sensory neurons and takes several hours to develop, showing hallmarks of long-term memory. Strikingly, O2 responses can be reprogrammed by experience in some genetic backgrounds but not others: a neuroglobin allele expressed in the O2 sensors and present in many wild strains functions to potently restrict plasticity. In this way, different alleles allow divergent behavioural strategies in reaction to sensory cues: responses can be either narrowly tuned and fixed to a certain concentration level, or broadly tuned and flexible in a changing environment.