Background: Ambient oxygen (O(2)) influences the behavior of organisms from bacteria to man. In C. elegans, an atypical O(2) binding soluble guanylate cyclase (sGC), GCY-35, regulates O(2) responses. However, how acute and chronic changes in O(2) modify behavior is poorly understood. Results: Aggregating C. elegans strains can respond to a reduction in ambient O(2) by a rapid, reversible, and graded inhibition of roaming behavior. This aerokinetic response is mediated by GCY-35 and GCY-36 sGCs, which appear to become activated as O(2) levels drop and to depolarize the AQR, PQR, and URX neurons. Coexpression of GCY-35 and GCY-36 is sufficient to transform olfactory neurons into O(2) sensors. Natural variation at the
npr-1 neuropeptide receptor alters both food-sensing and O(2)-sensing circuits to reconfigure the salient features of the C. elegans environment. When cultivated in 1% O(2) for a few hours, C. elegans reset their preferred ambient O(2), seeking instead of avoiding 0%-5% O(2). This plasticity involves reprogramming the AQR, PQR, and URX neurons. Conclusions: To navigate O(2) gradients, C. elegans can modulate turning rates and speed of movement. Aerotaxis can be reprogrammed by experience or engineered artificially. We propose a model in which prolonged activation of the AQR, PQR, and URX neurons by low O(2) switches on previously inactive O(2) sensors. This enables aerotaxis to low O(2) environments and may encode a "memory" of previous cultivation in low O(2).