Distinct activity-gated pathways mediate attraction and aversion to CO₂ in Drosophila

Carbon dioxide is produced by many organic processes and is a convenient volatile cue for insects that are searching for blood hosts, flowers, communal nests, fruit and wildfires. Although Drosophila melanogaster feed on yeast that produce CO₂ and ethanol during fermentation, laboratory experiments suggest that walking flies avoid CO₂. Here we resolve this paradox by showing that both flying and walking Drosophila find CO₂ attractive, but only when they are in an active state associated with foraging. Their aversion to CO₂ at low-activity levels may be an adaptation to avoid parasites that seek CO₂, or to avoid succumbing to respiratory acidosis in the presence of high concentrations of CO_2 that exist in nature. In contrast to CO₂, flies are attracted to ethanol in all behavioural states, and invest twice the time searching near ethanol compared to CO₂. These behavioural differences reflect the fact that ethanol is a unique signature of yeast fermentation, whereas CO₂ is generated by many natural processes. Using genetic tools, we determined that the evolutionarily conserved ionotropic co-receptor IR25a is required for CO₂ attraction, and that the receptors necessary for CO₂ avoidance are not involved in this attraction. Our study lays the foundation for future research to determine the neural circuits that underlie both state- and odorant-dependent decision-making in Drosophila. ; © 2018 Springer Nature Limited. Received: 22 December 2017; Accepted: 11 October 2018; Published online: 21 November 2018. We thank A. Straw for the 3D tracking software. Several colleagues provided mutants: R. Benton (quadruple mutant), R. Stanewsky (IR25a and rescue); G. Suh (IR8a); and M. Gallio and M. Stensmyr (IR40a). R. Benton, E. Hong and J. Riffell contributed helpful comments. This work was funded by grants from NIH (NIH1RO1DCO13693-01, U01NS090514) and the Simons Foundation. Reviewer information: Nature thanks S. Combes, M. Frye, L. Vosshall and R. Wilson for their contribution to the peer review of this work. Author ...