Neural Basis of Mosquito Host-Seeking

A single mosquito bite can be deadly. By biting humans, mosquitoes transmit pathogens responsible for malaria, yellow fever, Zika, and dengue, which together claim more than half a million lives each year. Only females bite, requiring a blood-meal for egg maturation, and rely on integrating sensory cues to locate hosts. Among these cues, carbon dioxide (CO2) from human breath plays a fundamental role. CO2 triggers activation, transforming behavior from undirected flight to sustained targeted upwind navigation, while simultaneously initiating sensitization, in which other modalities become primed to respond to cues such as body odor, heat, and visual contrast. Activation and sensitization initiate the host-seeking program that culminates in biting. The neural circuits driving host-seeking remain uncharacterized, as the tools to study mosquito central brain circuits have not existed until now. I developed a pipeline integrating whole-cell patch-clamp electrophysiology in a novel ex vivo Aedes aegypti brain explant with dye filling and connectome registration, linking the physiology of each recorded neuron to its synaptic connectivity. I identified distinct projection neuron and interneuron classes matching connectome-defined categories, and used two-photon photoactivation to identify CO2-dedicated projection neurons. This work lays the groundwork for understanding how the mosquito olfactory circuit generates the robust, sustained host-seeking that drives disease transmission.