From summer evenings to global disease prevention, mosquito repellents are a daily defense for billions of people, yet until now, scientists didn’t fully understand how mosquitoes themselves perceive these “keep away” signals. A new study has pinpointed an odorant receptor that helps mosquitoes detect a repellent odor and steer away. The researchers found that activating this receptor switches on a dedicated neural pathway that can override the insects’ attraction to human scents, producing clear avoidance behavior. By mapping the molecular and neural mechanism behind this response, the findings point to new strategies for designing more targeted and effective mosquito repellents.

For millenia, people have relied on plant extracts such as camphor and borneol to repel mosquitoes, but the biological mechanism behind their effectiveness has remained unclear. A new study led by Dr. Jonathan Bohbot of the Department of Entomology at the Hebrew University of Jerusalem in collaboration with researchers from Baylor University, the University of Washington, the University of California, the Swedish University of Agricultural Sciences, and additional international partners, has now identified the specific smell receptor that causes mosquitoes to actively avoid borneol, a natural compound found in camphor tree oils.

The international research team discovered that a highly conserved odorant receptor, known as OR49, is finely tuned to detect borneol in several major mosquito species, including Aedes aegypti and Culex mosquitoes, which are responsible for transmitting diseases such as dengue, Zika, and West Nile virus. Activation of this receptor triggers a neural pathway that leads mosquitoes to avoid the source of the odor.

Using genetic engineering alongside electrophysiological recordings, brain imaging, and behavioral experiments, the researchers showed that borneol activates a specialized sensory neuron in the mosquito’s maxillary palp, an organ central to host detection. Notably, this neuron sits beside the palp’s attraction-sensing neurons, those that help mosquitoes find humans by detecting carbon dioxide and other body odors, highlighting a built-in neural architecture that integrates repulsion signals alongside host-seeking cues. To speed identification of the most relevant natural activators of this pathway, the team turned to an unexpected source: cannabis essential oil. By screening and fractionating multiple cannabis oil preparations and using Or49 activation as a biological readout to guide purification, they connected complex plant mixtures to specific behaviorally active constituents and ultimately pinpointed borneol as the most potent Or49 activator in the study, directly linking plant chemistry to a precise mosquito sensory target.

Understanding how mosquitoes detect and respond to repellent odors is especially important as resistance to conventional chemical repellents grows and concerns rise over their environmental and health impacts. Targeting a mosquito’s own sensory wiring could allow researchers to develop repellents that are more precise, longer-lasting, and potentially less harmful to humans and ecosystems.

Behavioral tests confirmed the real-world relevance of the findings: mosquitoes exposed to borneol were significantly less likely to approach human skin and spent far less time nearby. When the OR49 receptor was genetically disabled, mosquitoes no longer responded to borneol, demonstrating that this single receptor is essential for the repellent effect.

“These results explain, at a molecular and neural level, why borneol has been used as a mosquito repellent for thousands of years,” said Dr. Bohbot. By pinpointing the exact receptor involved, we can begin to design more targeted and potentially safer repellents that exploit the mosquito’s own sensory system. The findings also link cutting-edge neurogenetics to deep human history: camphor- and borneol-rich materials, associated with sources in Borneo, were traded into China and carried westward along the Maritime Silk Road for their fragrance, medicinal value, and insect-deterring effects, and the newly identified Or49 pathway helps explain why these botanicals built such a durable reputation across centuries.

Beyond its practical implications, the study provides new insight into how mosquitoes integrate conflicting sensory cues from humans and plants, shaping their host-seeking behavior. This knowledge is especially valuable as researchers look for alternatives to conventional repellents, amid concerns about safety, environmental impact, and the need for longer-lasting protection. By turning a centuries-old plant-based remedy into a modern neurobiological blueprint, the study lays the groundwork for a new generation of mosquito control tools rooted in how insects actually detect and respond to odors.