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In mice, anxiety isn’t all in the

head. It can start in the heart
In high-risk contexts, a racing heart can make a formerly relaxed mouse nervous

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In scary situations — such as being faced with a big human shoe — a mouse might behave fearfully and its heart might race. Now, scientists have used light over a
mouse’s heart to make the animal behave fearfully, no big shoe required.
YAORUSHENG/MOMENT/GET TY IMAGES PLUS

By Bethany Brookshire
3 HOURS AGO

When you’re stressed and anxious, you might feel your heart race. Is your heart
racing because you’re afraid? Or does your speeding heart itself contribute to
your anxiety? Both could be true, a new study in mice suggests.

By artificially increasing the heart rates of mice, scientists were able to increase
anxiety-like behaviors — ones that the team then calmed by turning off a
particular part of the brain. The study, published in the March 9 Nature, shows
that in high-risk contexts, a racing heart could go to your head and increase
anxiety. The findings could offer a new angle for studying and, potentially,
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The idea that body sensations might contribute to emotions in the brain goes
back at least to one of the founders of psychology, William James, says Karl
Deisseroth, a neuroscientist at Stanford University. In James’ 1890 book The
Principles of Psychology, he put forward the idea that emotion follows what the
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body experiences. “We feel sorry because we cry, angry because we strike, afraid
because we tremble,” James wrote.

The brain certainly can sense internal body signals, a phenomenon called
interoception. But whether those sensations — like a racing heart — can
contribute to emotion is difficult to prove, says Anna Beyeler, a neuroscientist at Making Mice Mellow: Rodents
the French National Institute of Health and Medical Research in Bordeaux. She yield clues to improved anxiety
drugs
studies brain circuitry related to emotion and wrote a commentary on the new By Bruce Bower • October 2, 2002

study but was not involved in the research. “I’m sure a lot of people have thought
of doing these experiments, but no one really had the tools,” she says.

Deisseroth has spent his career developing those tools. He is one of the scientists
who developed optogenetics — a technique that uses viruses to modify the genes
of specific cells to respond to bursts of light (SN: 6/18/21; SN: 1/15/10). Scientists Groomed for Trouble: Mice yield
obsessive-compulsive insights
can use the flip of a light switch to activate or suppress the activity of those cells. By Bruce Bower • August 22, 2007

LIFE

Anxiety switch makes mice shy

no more
By Laura Sanders • March 9, 2011

Using tiny, custom-built vests outfitted with a light, scientists shined a red light over a mouse’s heart to affect its behavior.
RITCHIE CHEN, BRIAN HSUEH AND KARL DEISSEROTH/STANFORD UNIV.

In the new study, Deisseroth and his colleagues used a light attached to a tiny
vest over a mouse’s genetically engineered heart to change the animal’s heart
rate. When the light was off, a mouse’s heart pumped at about 600 beats per
minute. But when the team turned on a light that flashed at 900 beats per
minutes, the mouse’s heartbeat followed suit. “It’s a nice reasonable acceleration,
[one a mouse] would encounter in a time of stress or fear,” Deisseroth explains.

When the mice felt their hearts racing, they showed anxiety-like behavior. In risky
scenarios — like open areas where a little mouse might be someone’s lunch —
the rodents slunk along the walls and lurked in darker corners. When pressing a
lever for water that could sometimes be coupled with a mild shock, mice with
normal heart rates still pressed without hesitation. But mice with racing hearts
decided they’d rather go thirsty.

“Everybody was expecting that, but it’s the first time that it has been clearly
demonstrated,” Beyeler says.

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The researchers also scanned the animals’ brains to find areas that might be
processing the increased heart rate. One of the biggest signals, Deisseroth says,
came from the posterior insula (SN: 4/25/16). “The insula was interesting because
it’s highly connected with interoceptive circuitry,” he explains. “When we saw that
signal, [our] interest was definitely piqued.”

Using more optogenetics, the team reduced activity in the posterior insula, which
decreased the mice’s anxiety-like behaviors. The animals’ hearts still raced, but
they behaved more normally, spending some time in open areas of mazes and
pressing levers for water without fear.

This video shows a mouse’s heart beating normally. Then, when a light is switched and flickers at a speedy tempo, the
heart follows the rhythm and starts to race.

A lot of people are very excited about the work, says Wen Chen, the branch chief
of basic medicine research for complementary and integrative health at the
National Center for Complementary and Integrative Health in Bethesda, Md. “No
matter what kind of meetings I go into, in the last two days, everybody brought
up this paper,” says Chen, who wasn’t involved in the research.

The next step, Deisseroth says, is to look at other parts of the body that might
affect anxiety. “We can feel it in our gut sometimes, or we can feel it in our neck
or shoulders,” he says. Using optogenetics to tense a mouse’s muscles, or give
them tummy butterflies, might reveal other pathways that produce fearful or
anxiety-like behaviors.

Understanding the link between heart and head could eventually factor into how
doctors treat panic and anxiety, Beyeler says. But the path between the lab and
the clinic, she notes, is much more convoluted than that of the heart to the head.

Questions or comments on this article? E-mail us

at feedback@sciencenews.org | Reprints FAQ

CITATIONS
B. Hsueh et al. Cardiogenic control of affective behavioural state. Nature. Vol. 615, March 9, 2023, p. 292. doi:
10.1038/s41586-023-05748-8.

About Bethany Brookshire

Bethany was previously the staff writer at Science News for Students. She has a Ph.D. in physiology
and pharmacology from Wake Forest University School of Medicine.

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