How mosquito brains encode human odor so they can seek us out

Date:
May 4, 2022
Source:
Princeton University
Summary:
Some strains of Aedes aegypti -- the mosquito that carries Zika,
malaria and dengue fever -- have evolved to bite humans almost
exclusively. A team has now discovered how they target us so
precisely.



FULL STORY ========================================================================== Mosquitoes. Bane of backyard picnics -- and deadly in Zika- and
dengue-prone regions.


==========================================================================
Most of the world's mosquitos are opportunistic, willing to drink blood
from any nearby source. But in some regions, the mosquitoes that carry
Zika, dengue and yellow fever -- Aedes aegypti -- have evolved to bite
humans almost exclusively. But to succeed as a specialized feeder,
depending on just one species -- ours -- to survive, they must have
evolved incredibly precise targeting strategies. How do they do it?
"We set out to try to understand how these mosquitoes distinguish human
and animal odor," said Carolyn "Lindy" McBride, an assistant professor of ecology and evolutionary biology and neuroscience, "both in terms of what
it is about human odor that they cue in on and what part of their brain
allows them to cue in on those signals." After years of dedicated work, including countless scientific and technological challenges, her team
has discovered answers to both parts of this equation.

What is it that the mosquitos are detecting, and how do they detect
it? Their results appear in the current issue of Nature.

McBride described their mosquito-centric approach: "We sort of dove into
the brain of the mosquito and asked, 'What can you smell? What lights
up your brain? What's activating your neurons? And how is your brain
activated differently when you smell human odor versus animal odor?'" Then-graduate student Zhilei Zhao, a 2021 Ph.D. alumnus who is now at
Cornell, pioneered their novel approach: imaging mosquito brains at
very high resolution to watch how the mosquito identifies its next
victim. To do that, he had to first genetically engineer mosquitos
whose brains lit up when active, and then the team had to deliver human-
and animal-flavored air in ways that the mosquitos could detect while
inside the team's custom-built imaging equipment.



========================================================================== Human odor is composed of dozens of different compounds, and those same compounds, in slightly different ratios, are present in most mammal
odors. None of those compounds is attractive to mosquitoes by itself,
so the challenge was to determine the exact blend of components that
mosquitos use to recognize human odor.

The team concluded that two chemicals, decanal and undecanal, are
enriched in human odor. They patented a blend featuring decanal that
they hope could lead to baits attracting mosquitoes to lethal traps,
or repellents that interrupt the signal.

To provide comparison mammals to test, graduate student Jessica Zung
worked with former research specialists Alexis Kriete and Azwad Iqbal
to collect hair, fur and wool samples. For this paper, the team used
odor from sixteen humans, two rats, two guinea pigs, two quail, one
sheep and four dogs. Howell Living History Farm in Hopewell, N.J.,
donated several fleeces from their spring sheep shearing; for another domesticated mammal, Zung went to a grooming salon and gathered trimmed
hairs from recently groomed pet dogs.

"For the human samples, we had a bunch of great volunteers," Zung
said. "We had them not shower for a few days, then strip down naked
and lie down in a Teflon bag." Why naked? Because cotton, polyester and
other clothing fibers have their own smells that would distort the data.

Once they conquered the technical challenges -- retrieving the human
and animal odors nondestructively, designing a system that allowed them
to puff human odor at the mosquitos in the imaging setup, creating a
wind tunnel to test simple blends or single compounds, and breeding
viable strains of mosquitos whose brains respond to the equipment --
they began gathering data.



==========================================================================
Very surprising data.

Before this study, researchers speculated that mosquito brains must have
a complicated, sophisticated technique for distinguishing humans from
other animals. Quite the opposite, it turned out.

"The simplicity surprised us," said McBride. "Despite the complexity
of human odor, and the fact that it doesn't really have any kind of human-specific compounds in it, the mosquitoes have evolved a surprisingly simple mechanism for recognizing us. To me, it's an evolutionary story:
if we created a statistical test to differentiate human odor, it would
be very complex, but the mosquito does something remarkably simple, and
simple usually works pretty well, when it comes to evolution." In other
words, simple solutions tend to breed true, over evolutionary time.

Mosquito brains have 60 nerve centers called glomeruli (singular:
glomerulus).

The team had hypothesized that many -- maybe even most -- would be
involved in helping these human-dependent mosquitos find their favorite
food.

"When I first saw the brain activity, I couldn't believe it -- just two glomeruli were involved," Zhao said. "That contradicted everything we
expected, so I repeated the experiment several times, with more humans,
more animals. I just couldn't believe it. It's so simple." Of the
two nerve centers, one responds to many smells including human odor, essentially saying, "Hey, look, there's something interesting nearby you
should check out," while the other responds only to humans. Having two
may help the mosquitos home in on their targets, the researchers suggest.

That was one of the biggest "Eureka!" moments in the project, said
McBride.

"Zhilei had worked for a couple years to get the transgenic mosquitoes
that he needed, and then we found that we didn't have a good way to
deliver human odor.

So we worked for another year or two, coming up with ideas to try to
figure out how to deliver enough human odor in a controlled enough way
to see a response.

Then, the first time we tried this new technology that we described
in the paper -- this new way of delivering odors -- he actually saw a
brain respond.

It was incredible." By determining the glomeruli that mosquitos use to
detect humans, and identifying what it is they are detecting -- decanal
and undecanal -- the team has an elegantly straightforward answer to
their questions, noted Zung.

"If this were purely a neuro imaging paper, there would be some questions remaining," she said. "If this were purely an odor analysis paper,
there would still be unanswered questions. A purely behavior paper,
same thing. But one real strength of this project is that we were able
to bring in so many different methods and the expertise of so many
people. And Lindy was just amazing and willing to learn about and invest
in all these different methods." "This entire project is incredibly collaborative," Zhao agreed. "We were tackling so many lines of evidence
that have now converged into a cohesive story, and that requires so much different expertise. I hadn't studied any neuroscience before I came
to Princeton, but we have the Princeton Neuroscience Institute here,
with so many talented people I could learn from. For the odor science
part, I have no background in that, but Jessica is an expert. And for the
wind tunnel setup, we collaborated with researchers in Sweden. If we had
done everything ourselves, we might not have gotten such good results;
it's only through collaboration that we got here."

========================================================================== Story Source: Materials provided by Princeton_University. Original written
by Liz Fuller- Wright. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Zhilei Zhao, Jessica L. Zung, Annika Hinze, Alexis L. Kriete, Azwad
Iqbal, Meg A. Younger, Benjamin J. Matthews, Dorit Merhof,
Stephan Thiberge, Rickard Ignell, Martin Strauch, Carolyn
S. McBride. Mosquito brains encode unique features of human odour
to drive host seeking.

Nature, 2022; DOI: 10.1038/s41586-022-04675-4 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/05/220504130829.htm

--- up 9 weeks, 2 days, 10 hours, 51 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)