Abstract

Sensory behaviors are often flexible, allowing animals to generate context-appropriate responses to changing environmental conditions. To investigate the neural basis of behavioral flexibility, we examined the regulation of carbon dioxide (CO₂) response in the nematode Caenorhabditis elegans. CO₂ is a critical sensory cue for many animals, mediating responses to food, conspecifics, predators, and hosts (Scott, 2011; Buehlmann et al., 2012; Chaisson and Hallem, 2012). In C. elegans, CO₂ response is regulated by the polymorphic neuropeptide receptor NPR-1: animals with the N2 allele of npr-1 avoid CO₂, whereas animals with the Hawaiian (HW) allele or an npr-1 loss-of-function (lf) mutation appear virtually insensitive to CO₂ (Hallem and Sternberg, 2008; McGrath et al., 2009). Here we show that ablating the oxygen (O₂)-sensing URX neurons in npr-1(lf) mutants restores CO₂ avoidance, suggesting that NPR-1 enables CO₂ avoidance by inhibiting URX neurons. URX was previously shown to be activated by increases in ambient O₂ (Persson et al., 2009; Zimmer et al., 2009; Busch et al., 2012). We find that, in npr-1(lf) mutants, O₂-induced activation of URX inhibits CO₂ avoidance. Moreover, both HW and npr-1(lf) animals avoid CO₂ under low O₂ conditions, when URX is inactive. Our results demonstrate that CO₂ response is determined by the activity of O₂-sensing neurons and suggest that O₂-dependent regulation of CO₂ avoidance is likely to be an ecologically relevant mechanism by which nematodes navigate gas gradients.