The yellow fever mosquito Aedes aegypti employs olfaction to locate humans. We applied neural activity mapping to define the molecular and cellular logic of how the mosquito brain is wired to detect two human odorants that are attractive when blended together. We determined that the human breath volatile carbon dioxide (CO2) is detected by the largest unit of olfactory coding in the antennal lobe of the mosquito brain. Synergistically, CO2 detection gates pre-synaptic calcium signaling in olfactory sensory neuron axon terminals that innervate unique antennal lobe regions tuned to the human sweat odorant L-(+)-lactic acid. We propose that simultaneous detection of the signature human volatiles CO2 and L-(+)-lactic acid disinhibits a multimodal olfactory network for hunting humans in the mosquito brain.
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