Female yellow fever mosquitoes can smell you from more than 100 feet away, and just a whiff of your breath likely enhances their vision and triggers a flight response that can send the bloodsuckers homing after you, according to new research from the University of Washington.

“What their sense of smell is doing is telling them there’s something there to investigate,” said Jeff Riffell, a UW professor of biology and part of the research team examining what attracts Aedes aegypti mosquitoes to people. “The vision tells them where the source of the scent is located.”

As part of this research, the scientists tethered mosquitoes to a tiny wire, placed them in a flight simulator arena with hundreds of controlled LED lights and measured their responses.

In a separate experiment, the researchers secured genetically modified mosquitoes to a platform by their sliced-open heads and used a microscope to watch their brain matter glow fluorescent green as neural activity was triggered.

The research, which was published in the peer-reviewed journal Current Biology on Thursday, could help researchers develop tools to control or eradicate populations of Aedes aegypti mosquitoes, a public health menace that spreads viruses that cause yellow fever, dengue fever, West Nile and Zika. The mosquitoes are expanding their range as global temperatures rise.

The research, which relies on rapidly developing techniques for gene modification, also expands scientists’ understanding of insect cognition.

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Aedes aegypti mosquitoes “carry a lot of viruses that are detrimental to human health,” said Chris Potter, an associate professor of neuroscience at Johns Hopkins School of Medicine who studies mosquitoes but was not involved in this research. “With global warming and climate change, the regions these mosquitoes can cover are becoming broader.”

Tethered Aedes aegypti mosquito flying in the arena.  (Kiley Riffell)
Tethered Aedes aegypti mosquito flying in the arena. (Kiley Riffell)

Potter added that the research was credible, novel and also “opens up a whole new avenue of experiments” because the researchers were able to demonstrate that it was possible to peer into mosquitoes’ brains during tests.

Only female mosquitoes suck blood from their hosts. Riffell and the other researchers performed two separate types of experiments on female mosquitoes for this study.

In the first experiment, the researchers used a thin wire pin to secure the mosquitoes inside the flight simulator, a roughly 10-by-15-inch cylinder lined with lights.

“You cool down the mosquitoes and then you put them on ice for a few minutes and they go to sleep. And under a microscope, you use a little pin and UV glue,” Riffell said.

When ultraviolet light is shined on the glue, the epoxy hardens and fixes the pin to the body of the mosquito. Inside the arena, the mosquito is able to flap its wings, but remains stuck in place.

Lights in the flight simulator represent different visual objects to tethered mosquitoes.   (Kiley Riffell)
Lights in the flight simulator represent different visual objects to tethered mosquitoes. (Kiley Riffell)

Rows of light-emitting diodes surround the stationary insect. An infrared light that the creature cannot see creates shadows that scientists can capture with a wingbeat-analyzing device. The mosquito is placed between an air inlet and vacuum, which allowed scientists to create a flow of carbon dioxide, to mimic human respiration and signal to mosquitoes that their food might be near.

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During experiments on about 250 mosquitoes, the researchers would give the insects a puff of carbon dioxide and also create shapes and displays in the LED lights.

Riffell said humans have vision perhaps a hundred or a thousand times better than mosquitoes, so the LED lights provide a sufficient display. At a distance, a person wearing a black shirt will appear to a mosquito as a dark bar, he said.

The scientists found that a puff of carbon dioxide odor caused mosquitoes to beat their wings faster. When a dark, moving bar was projected inside the flight simulator, the creatures would flap harder and try to steer toward it.

But without the smell of carbon dioxide, the creatures reacted weakly to the moving bar alone.

Later, the scientists performed similar tests with mosquitoes that were pinned to a 3D-printed station. These insects had been genetically modified so cells would grow fluorescent green when neurons were activated.

“We cut this little hole in their head capsule,” Riffell said, and peered into the mosquitoes’ brains with a microscope as they flapped around.

When the live mosquitoes were given a puff of carbon dioxide, the scientists watched as the optical areas of the mosquitoes’ brains fired up with neural activity.

In other words, the smell of human breath could activate and enhance mosquitoes’ ability to see you and suck your blood.

“It’s triggering something in the brain that allows the mosquito to be better at finding humans,” Potter said.

The research could open doors to eradicating mosquitoes and preventing their diseases, Potter added.

“If we could figure out how olfactory neurons are working, we could guide their behavior.”

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Scientists could develop particular smells to lure and kill them, lay their eggs in insecticide traps or develop more effective insect repellents, he said.

Calcium imaging captures neuron activity in tethered Aedes aegypti mosquitoes. (Kiley Riffell)
Calcium imaging captures neuron activity in tethered Aedes aegypti mosquitoes. (Kiley Riffell)

Areas of research like Riffell’s, which relies upon genetic modification to provide a new window into the brain, are developing rapidly with improving technology.

It began with fruit flies, said Mark Frye, a professor of integrative biology and physiology at the University of California Los Angeles.

“Molecular tools to target regions of the genome were created,” Frye said. “In the last 10 years, that effort has exploded.”

Now groups are expanding these techniques to other kinds of insects and making new discoveries. Frye said scientists increasingly understand that animals’ senses might be wired together and working in concert.

“If you watch a honeybee forage around in the flower garden, the more you watch one of these animals, the more you realize, they really know what they’re doing, they’re really clever, and yet they have this brain that’s so numerically compact, it defies logic,” Frye said. “Maybe we’re just scratching the surface of how the brain really functions.”