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bioRxiv · 10.1101/2025.07.29.667487

Recurrent connectivity supports carbon dioxide sensitivity in Aedes aegypti mosquitoes

Bao, J.·Alford, W.·Khandelwa, A.·Walsh, L.·Lantz, G.·Poncio, S.·Capdevila, L. S.·Azatian, Y.·DePasquale, B.·Hildebrand, D. G.·Younger, M. A.·Lee, W.-C. A.
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Abstract

The mosquito Aedes aegyptis human host-seeking behavior depends on the integration of multiple sensory cues. One of these cues, carbon dioxide (CO2), gates odorant and heat pathways and activates host-seeking behavior. The neuronal circuits underlying processing of CO2 information remain unclear. We used automated serial-section transmission electron microscopy (EM) to image and reconstruct the circuitry of the glomeruli that are innervated by the Ae. aegypti maxillary palp, including the glomerulus that responds to CO2. Notably, CO2-sensitive olfactory sensory neurons (OSNs) make high levels of recurrent synaptic connections with one another, while making a low density of feedforward synapses. At some of these contacts between CO2 OSNs, we observe ribbon- like presynaptic structures, which may further enhance recurrent signaling. We compared both feedforward and recurrent connectivity with all olfactory glomeruli in Drosophila melanogaster, and we found more recurrent connections between the Ae. aegypti CO2-responsive OSNs than in any D. melanogaster glomeruli. We developed a computational circuit model that demonstrates recurrent synapses are necessary for robust CO2 detection under normal physiological conditions. Together, elevated levels of recurrent connectivity and ribbon-like structures may amplify sensory information detected by CO2-sensitive OSNs to support mosquito activation and sensitization by CO2, even in the presence of high levels of other odorants in the environment. We propose that this circuit organization supports the salience of CO2 as a mosquito host cue. One Sentence SummaryConnectomic analysis of carbon dioxide circuitry in the disease-vector mosquito Aedes aegypti.

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Bao, J., Alford, W., Khandelwa, A., Walsh, L., Lantz, G., Poncio, S., Capdevila, L. S., Azatian, Y., DePasquale, B., Hildebrand, D. G., Younger, M. A., Lee, W.-C. A.. 2025-07-30. Recurrent connectivity supports carbon dioxide sensitivity in Aedes aegypti mosquitoes. https://doi.org/10.1101/2025.07.29.667487

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