Ultra-prolonged activation of CO ₂-sensing neurons disorients mosquitoes

Summary

CO ₂ present in exhaled air is the most important sensory cue for female blood-feeding mosquitoes, causing activation of long-distance host-seeking flight, navigation towards the vertebrate host ¹ , and, in the case of Aedes aegypti, increased sensitivity to skin odours ² . The CO ₂ detection machinery is therefore an ideal target to disrupt host seeking. We use electrophysiological assays to identify a volatile odourant that causes an unusual, ultra-prolonged activation of CO ₂-detecting neurons in three major disease-transmitting mosquitoes: Anopheles gambiae, Culex quinquefasciatus and A. aegypti. Importantly ultra-prolonged activation of this neuron severely compromises its ability to subsequently detect CO ₂ for several minutes. We also identify odours that strongly inhibit the CO ₂-sensitive neuron as candidates for use in disruption of host-seeking behaviour, as well as an odour that evokes CO ₂-like activity and thus has potential use as a lure in trapping devices. Analysis of responses to panels of structurally related odours across the three mosquitoes and Drosophila, which have related CO ₂-receptor proteins, reveals a pattern of inhibition that is often conserved. We use video tracking in wind-tunnel experiments to demonstrate that the novel ultra-prolonged activators can completely disrupt CO ₂-mediated activation as well as source-finding behaviour in Aedes mosquitoes, even after the odour is no longer present. Finally, semi-field studies demonstrate that use of ultra-prolonged activators disrupts CO ₂-mediated hut entry behaviour of Culex mosquitoes. The three classes of CO ₂ response modifying odours offer powerful instruments for developing new generations of insect repellents and lures, which even in small quantities can interfere with the ability of mosquitoes to seek humans.