Into the Brains of Mosquitoes – Finding out how they find us

Featured Image Caption: Aedes aegypti mosquitoes specialize in finding human hosts for blood meals, and scientists have discovered how their brain decodes human scent (Image Credit: “Aedes aegypti mosquito” by Sanofi Pasteur is licensed under CC BY-NC-ND 2.0.).

Reference: Zhao, Z., Zung, J. L., Hinze, A., Kriete, A. L., Iqbal, A., Younger, M. A., Matthews, B. J., Merhof, D., Thiberge, S., Ignell, R., Strauch, M., & McBride, C. S. (2022). Mosquito brains encode unique features of human odour to drive host seeking. Nature, 605, 706-712.

Nice weather calls for outdoor fun. Day or night – whether hiking, camping, fishing, etc. – it’s usually only a matter of time before a faint buzz passes the ear, often followed by familiar small bites. Before you know it, the party has multiplied some unwanted guests: the mosquitoes. Seeming to arrive out of nowhere, one might question how the mosquitoes found them. And, out of all the other animals outside, why do the mosquitoes flock to humans? Scientists took these questions head-on by examining the brains of mosquitoes to see how they use odors to seek and distinguish humans from other animals. They found that mosquitoes turn scents into signals in just three brain regions.

What’s That Smell?

Mosquitoes (Aedes aegypti) have expanded globally with the help of humans, often hitchhiking on ships to other continents. Over time, forming close associations with dense human populations has led mosquitoes to specialize in biting humans for their blood meals. However, only females bite humans, as they need the added protein in our blood to produce eggs. Males, on the other hand, can survive on sugary plant secretions, like nectar. Female mosquitoes have become experts at seeking, identifying, and discriminating between hosts. Besides an itchy bite, females could pass along viral diseases, such as dengue, yellow fever, and Zika, while taking their meals. Understanding how mosquitoes find human hosts can give insight into ways to control mosquito populations and the viruses they carry.

Aedes aegypti mosquitoes have quickly spread across the globe with help from human travelers. The color indicates the probability of occurrence from 0 to 1 (Image Credits:  “File:Global Aedes aegypti distribution (e08347).png” by Moritz UG Kraemer, Marianne E Sinka, Kirsten A Duda, et al. is marked with CC0 1.0).

Female mosquitoes likely use several cues to locate potential hosts. They can use carbon dioxide (exhaled air) and body temperature to identify a living thing as a vertebrate, but odor cues are required to distinguish between humans and animals. Mosquitoes use their antennae and mouthparts to access smells that float through the air. These scents can be very challenging to study because the compounds are often complex and in varying ratios. Learning how the brain processes the odors sensed by the mosquito is an additional feat but one that researchers Zhilei Zhao and colleagues were ready to take on.    

Turning Scent into Signal
Females rely on protein-rich human blood to produce eggs while males can survive on nectar from plants (Image Credit: Top: “Aedes Aegypti” by Marcos Teixeira de Freitas is licensed under CC BY-NC 2.0; Bottom: “Mosquito II (Aedes Aegypti)” by Marcos Teixeira de Freitas is licensed under CC BY-NC 2.0.).

The researchers first wanted to see how the mosquito’s brain helps it discriminate between humans and non-human animals that are often closely associated with humans. Presented with rat, sheep, and human smells, the mosquitoes’ first task was to choose a scent while the researchers observed what parts of the brain were activated. Since this mosquito species has recently evolved to specialize in feeding on humans, the researchers stuck with testing mammals, although other species can feed on non-mammals. When they provided these scents, they found three brain areas activated under different circumstances. The B (broadly tuned) region was activated whenever an animal or human scent was present. The A (animal-sensitive) and H (human-sensitive) areas were exclusively activated when in the presence of a non-human animal or human scent, respectively. Thus, the mosquitoes use the B region to decipher between vertebrate and non-vertebrate, and the H and A regions to identify humans from animals.

Next, the researchers wanted to see what chemicals in human odors activated this brain region. They scanned the compounds in human scent and identified those that made up at least 2% of the scent cocktail. While they found many highly abundant chemicals, one that stood out was a molecule with a long chain of carbon atoms (called decanal) that was more abundant in humans than animals. Most compounds in odors are shared between humans and animals, but the ratio of the compounds appears to differentiate the two. When the researchers provided these abundant human scents to mosquitoes, the H (human-sensitive) brain region was highly activated, especially for the long carbon chains.

Mosquito Minds Can Find

Mosquitoes first identify a potential host by activating the brain’s B (broadly tuned) area. More specific activations in the A (animal-sensitive) and H (human-sensitive) regions occur based on ratios of compounds unique to non-human animals or humans. Long chains of carbon atoms are really good at activating the H region, indicating to the mosquito that a protein-rich meal is nearby. These human odors are emitted by oily skin secretions – called sebum – that arise from hair follicles rather than sweat. Mosquitoes have cued in on sebum because it is a reliable scent that is always present whether a human is moving or resting.

When female mosquitoes bite, they can pass viruses to their human hosts. Understanding how mosquitoes find hosts can help develop better control strategies (Image Credit: “Aedes aegypti mosquito” by Sanofi Pasteur is licensed under CC BY-NC-ND 2.0.).

The researchers also found that mosquitoes were more likely to bite humans with an average amount of long carbon chain compounds than those with higher or lower levels than average. Scientists question whether this makes some people more prone to mosquito bites. A better understanding of how mosquitoes integrate human odor information may help design better control strategies that can help reduce dangerous mosquito-borne illnesses.

While scientists work to explain the brain, here are some tips to help you fight the bite.

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Brandi Pessman

I am a third-year Ph.D. student at the University of Nebraska-Lincoln in the School of Biological Sciences. Growing up on a farm in a small town in Illinois, I developed an early love for animals and a fascination with their behaviors. When I was younger, however, it never crossed my mind that I would be using spiders to investigate how human presence affects animal behavior, but I am loving every second of it. Studying the behaviors of animals can tell us a lot about the role that we play in their survival (or death), which is becoming increasingly important as human populations continue to grow. When I am not studying spiders, I enjoy playing with my cat or being outdoors!

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