In mice, anxiety isn’t just in the head. It can start in the heart

When you are stressed and anxious, you may feel your heart racing. Your heart races because you are afraid? Or is your racing heart itself contributing to your anxiety? Both could be true, suggests a new study in mice.

By artificially increasing the heart rate of mice, scientists were able to increase anxious behavior – those that the team then calmed down by turning off a particular part of the brain. The study, published on March 9 Nature, shows that in high-risk settings, a racing heart can go to your head and increase anxiety. The findings could offer a new angle for studying and, potentially, treating anxiety disorders.

The idea that bodily sensations might contribute to emotions in the brain goes back at least to one of psychology’s founders, William James, says Karl Deisseroth, a neuroscientist at Stanford University. In James’s 1890 book The principles of psychology, he put forward the idea that emotion follows what the body experiences. “We’re sorry because we cry, angry because we hit, scared because we shake,” James wrote.

The brain can certainly detect internal signals from the body, a phenomenon called interoception. But it’s hard to prove whether these sensations — like a racing heart — can contribute to emotion, says Anna Beyeler, a neuroscientist at France’s National Institute of Health and Medical Research in Bordeaux. She studies brain circuitry related to emotion and wrote a commentary on the new study, but was not involved in the research. “I’m sure a lot of people thought about doing these experiments, but no one really had the tools,” she says.

Deisseroth has spent his career developing these 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 flashes of light (SN: 06/18/21; SN: 01/15/10). Scientists can use the flip of a switch to turn these cells on or off.

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

When the mice felt their hearts racing, they exhibited anxious behavior. In risky scenarios — like open areas where a little mouse might be someone’s lunch — rodents slithered along walls and hid in darker corners. When pressing a lever for water that could sometimes be coupled with a mild shock, mice with normal heartbeats always pressed without hesitation. But the heart-pounding mice preferred to be thirsty.

“Everyone expected it, but this is the first time it’s been clearly demonstrated,” says Beyeler.

The researchers also scanned the animals’ brains to find areas that might treat the increased heart rate. One of the biggest signals, says Deisseroth, came from the posterior insula (SN: 04/25/16). “The insula was interesting because it is closely linked to the interoceptive circuits,” he explains. “When we saw this signal, [our] interest was definitely piqued.

By using more optogenetics, the team reduced activity in the posterior insula, which decreased the mice’s anxious behaviors. The animals’ hearts still raced, but they behaved more normally, spending time in open areas of mazes and pressing levers to obtain water without fear.

Many people are very excited about the work, says Wen Chen, head of the basic medicine research branch for complementary and integrative health at the National Center for Complementary and Integrative Health in Bethesda, Md. “It doesn’t matter what kind of meetings I attend over the past two days, everyone has presented this document,” says Chen, who was not involved in the research.

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

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