Recurrent synapses between CO₂-sensitive olfactory sensory neurons enable robust CO₂ detection in Aedes aegypti mosquitoes
7 affiliations
- 1Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, United States of America
- 2Molecules, Cells, and Organisms Training Program, Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, United States of America
- 3Department of Biology, Boston University, Boston, Massachusetts, United States of America
- 4Department of Biomedical Engineering, Boston University, Boston, Massachusetts, United States of America
- 5Laboratory of Neural Systems, The Rockefeller University, New York, New York, United States of America
- 6Department of Vision Sciences, College of Optometry, University of Houston, Houston, Texas, United States of America
- 7F.M. Kirby Neurobiology Center, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
Abstract
The mosquito Aedes aegypti’s 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.
Carbon dioxide is among the most important cues used by Aedes aegypti mosquitoes when searching for a human blood meal. This study shows that the wiring of the neurons that sense carbon dioxide differs from the wiring in Drosophila to support robust detection of this ethologically key host cue.
Related
- SNMP1 Contributes to Sensitive Pheromone and Plant Volatile Detection in the Locust Olfactory System
- Recurrent beta-gamma interactions between olfactory bulb and piriform cortex support cross-sniff perceptual continuity in humans
- From Passive Drift to Olfactory Detection? A Late‐Stage Oceanic Juvenile Hawksbill's 9000‐km Journey Across the Western Indian Ocean
- UniqSketch: sensitive and resource-efficient strain-level detection in metagenomes
- Development of Loop-Mediated Isothermal Amplification Assays for Rapid and Sensitive Detection of Three Viruses Infecting Areca catechu L.
BibTeX
@article{bao2026recurrent,
title = {{Recurrent synapses between CO₂-sensitive olfactory sensory neurons enable robust CO₂ detection in Aedes aegypti mosquitoes}},
author = {Jialu Bao and Wesley Alford and Avinash Khandelwal and Laurel Walsh and George Lantz and Santiago Poncio and Laia Serratosa Capdevila and Yervand Azatian and Brian DePasquale and David G. C. Hildebrand and Meg A. Younger and Wei-Chung Allen Lee},
journal = {PLOS Biology},
year = {2026},
month = sep,
doi = {10.1371/journal.pbio.3003959},
url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003959},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Recurrent synapses between CO₂-sensitive olfactory sensory neurons enable robust CO₂ detection in Aedes aegypti mosquitoes
AU - Jialu Bao
AU - Wesley Alford
AU - Avinash Khandelwal
AU - Laurel Walsh
AU - George Lantz
AU - Santiago Poncio
AU - Laia Serratosa Capdevila
AU - Yervand Azatian
AU - Brian DePasquale
AU - David G. C. Hildebrand
AU - Meg A. Younger
AU - Wei-Chung Allen Lee
PY - 2026
DA - 2026/09/10
JO - PLOS Biology
DO - 10.1371/journal.pbio.3003959
UR - https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003959
AB - The mosquito Aedes aegypti’s 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. Carbon dioxide is among the most important cues used by Aedes aegypti mosquitoes when searching for a human blood meal. This study shows that the wiring of the neurons that sense carbon dioxide differs from the wiring in Drosophila to support robust detection of this ethologically key host cue.
SN - 1545-7885
ER -