Circadian Control of Olfactory-Guided Behavior in Mosquitoes: From Host Detection to Repellency

Abstract

Biological rhythms are a pervasive feature of life and shape many aspects of mosquito biology, including locomotion, sensory responsiveness, host-seeking, and feeding behavior. Because mosquito-borne disease transmission depends on successful contact between female mosquitoes and their hosts, understanding how time of day shapes mosquito sensory behavior is important for both vector biology and disease control. However, the role of temporal regulation in mosquito olfactory behavior and mosquito-host chemical interactions remains unclear. In this dissertation, we first reviewed current knowledge on the daily and circadian regulation of insect olfaction and identified key open questions in the field. We then designed artificial quantitative chemical blend variants informed by subtle yet consistent variations in human odor and biased toward human odor profiles at specific times of the day. We found that female Aedes aegypti exhibit phase-dependent olfactory preferences for these blend variants. These behavioral patterns were altered under constant darkness and in mosquitoes lacking the core clock gene timeless, indicating that both environmental light cues and the circadian clock contribute to temporal variation in olfactory behavior. Transcriptomic analyses further revealed daily changes in gene expression in mosquito antennae (i.e., their main olfactory appendages), providing insight into the molecular basis of these rhythms. Finally, we evaluated a DEET-free repellent, Mozzie Wackka, across multiple mosquito species and behavioral assays, and found that it significantly reduced blood feeding, induced strong short-range avoidance, and exhibited greater persistence than DEET under the conditions tested. Together, these findings show that mosquito olfactory behavior is temporally dynamic, provide new insight into mosquito biology, and highlight the need to consider the temporal dimensions of mosquito biology in vector control strategies.