DEET Olfactory Reception in the Yellow Fever Mosquito

Developed almost 80 years ago, DEET is the first line of defense against the transmission of vector-borne diseases, and yet its mode of action is still a matter of controversy. Here we identified a dedicated odorant receptor that underlies DEET’s detection as a spatial repellency for the yellow fever mosquito Aedes aegypti. Using heterologous expression systems, we show that this receptor is finely tuned to DEET. CRISPR-mediated disruption impaired DEET-evoked neural activity in a defined olfactory sensillum and markedly reduced spatial avoidance at behaviorally relevant concentrations. Fluorescence-guided single-sensillum recordings revealed that DEET selectively activates a distinct olfactory sensory neuron population that projects to a single, defined glomerulus in the antennal lobe, establishing a direct receptor-to-circuit link for repellency coding. These findings uncover a dedicated sensory pathway for volatile repellent detection, revealing an unexpected specialization for a manmade chemical and providing a mechanistic framework for receptor-guided development of next-generation spatial repellents.