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A racing heart drives anxiety behavior in mice

NOMIS Awardee Karl Deisseroth and colleagues have found that when they increased heart rates in mice, the animals showed more anxious behavior. Their research was published in Nature.

Using pulses of light to control heart rate, Stanford Medicine researchers investigate a long-standing mystery about how physical states influence emotions.

By Nina Bai

Standing on the edge of a precipice, losing your way in a dark forest or running into a crush will quicken your pulse — a physical consequence of the anxiety you experience. But a new study in mice by Stanford Medicine scientists has found evidence of the reverse: A faster heart rate can generate anxiety.

When researchers artificially boosted an animal’s heart rate (the number of times a heart beats each minute), it behaved more cautiously in risky situations. The researchers traced the change to a particular region of the cortex, which appears to integrate heart rate with the brain’s perception of danger to determine the appropriate emotional response.

The findings address a question that has intrigued philosophers and scientists for more than a century: whether bodily sensations follow emotion, or the other way around. In 1884, the philosopher and early psychologist William James argued that, contrary to common belief, our emotional reaction to a situation comes after our physical reactions. “We feel sorry because we cry, angry because we strike, afraid because we tremble,” he wrote.

Karl Deisseroth

“William James felt that bodily states actually represent the emotions in a fundamental sense,” said Karl Deisseroth, MD, PhD, a professor of bioengineering and of psychiatry and behavioral sciences. Deisseroth is the senior author of a study, published March 1 in Nature, that employed the latest advances in optogenetics — using light to activate specific cells — to test the hypothesis.

Co-first authors of the study were Brian Hsueh, a graduate student, and Ritchie Chen, PhD, a postdoctoral fellow, both in Deisseroth’s lab.

Deisseroth first pondered the question as a psychiatry resident, when he learned that certain cardiac diseases correlate with anxiety disorders — but nobody knew why. James’s belief “was really intriguing,” he said, “but it was hard to test because one would have to impose, very precisely, the bodily state first, which has been essentially impossible to do.”

Lighting up the heart

Until the latest optogenetics approach, methods for changing a heart rate, such as electrical pacemakers or stimulant drugs, lacked precision or required invasive procedures.

Fortunately, Deisseroth, the D. H. Chen Professor, has spent the last 20 years pioneering the field of optogenetics, developing techniques that have allowed scientists to precisely control specific cell types in living animals. The method relies on genetically altering these cells to produce opsin, a protein that responds to light.

A few years ago, Deisseroth’s lab discovered an extra-sensitive opsin, called ChRmine, that can make even cells deep within the body respond to light from outside the body.

In the new study, researchers used ChRmine to control cardiomyocytes — the cells responsible for contractions of the heart. By genetically altering a mouse’s cardiomyocytes to produce ChRmine, the researchers were able to precisely control the animal’s heartbeat with external light.

“We really wanted a method where the animal could move freely while experiencing internal states, and to do that while illuminating the beating heart, we had to have the light coming from outside the body,” Deisseroth said.

Continue reading this Stanford Medicine release: A racing heart drives anxiety behavior in mice, Stanford Medicine researchers find

Read the Nature publication: Cardiogenic control of affective behavioural state


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D.H. Chen Professor of Bioengineering and of Psychiatry and Behavioral Sciences
Stanford Medicine
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