Interleukin 17 (IL-17) is a major pro-inflammatory cytokine: it mediates responses to pathogens or tissue damage, and drives autoimmune diseases. Little is known about its role in the nervous system. Here we show that IL-17 has neuromodulator-like properties in C. elegans. IL-17 can act directly on neurons to alter their response properties and contribution to behavior. Using unbiased genetic screens we delineate an IL-17 signaling pathway and show that it acts in the RMG hub interneurons. Disrupting IL-17 signaling reduces RMG responsiveness to input from O2-sensors, and renders sustained escape from 21% O2 transient and contingent on additional stimuli. Over-activating IL-17 receptors abnormally heightens responses to 21% O2 in RMG neurons and whole animals. IL-17 deficiency can be bypassed by optogenetic stimulation of RMG. Inducing IL-17 expression in adults can rescue mutant defects within 6 hours. These findings reveal a non-immunologic role of IL-17 modulating circuit function and behavior.

Brains organize behavior and physiology to optimize the response to threats or opportunities. We dissect how 21% O2, an indicator of surface exposure, reprograms C. elegans' global state, inducing sustained locomotory arousal and altering expression of neuropeptides, metabolic enzymes, and other non-neural genes. The URX O2-sensing neurons drive arousal at 21% O2 by tonically activating the RMG interneurons. Stimulating RMG is sufficient to switch behavioral state. Ablating the ASH, ADL, or ASK sensory neurons connected to RMG by gap junctions does not disrupt arousal. However, disrupting cation currents in these neurons curtails RMG neurosecretion and arousal. RMG signals high O2 by peptidergic secretion. Neuropeptide reporters reveal neural circuit state, as neurosecretion stimulates neuropeptide expression. Neural imaging in unrestrained animals shows that URX and RMG encode O2 concentration rather than behavior, while the activity of downstream interneurons such as AVB and AIY reflect both O2 levels and the behavior being executed.DOI: http://dx.doi.org/10.7554/eLife.04241.001

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