DDuring feelings of anxiety, the brain gives a boost to the heart. But while racing, does the heart, in turn, talk to the brain? For centuries scientists have debated whether the heart prevails over the mind, and now research published today (March 1) in Nature suggests that physical states can influence emotional states. The study found that high heart rate can cause anxious behaviors in mice, but only under risky circumstances. This suggests that interventions that target the heart could be effective treatments for panic disorders, the authors suggest.
“I thought it was a very elegant demonstration of what we instinctively believe and have shown using sketchy methods: that bodily states inform emotional states,” says Sarah Garfinkela cognitive neuroscientist from University College London who was not involved in the work.
In his 1884 trial “What is an emotion?” philosopher and psychologist William James, widely considered the founder of American psychology, argues that emotions are inextricably linked to bodily responses. Physiological changes, he writes, are the “raw material” of emotion, to which the brain assigns meaning, such as fear, surprise or excitement.
Since then, studies have suggested, albeit indirectly, that the heart is capable of sending frightening signals to the brain, says Garfinkel. But because the heart-brain connection is a two-way street, “it’s very difficult to disentangle what drives emotional states,” she adds. “Is it emotion that makes the heartbeat change or is it [the emotion] a consequence of the changing heart rate? »
Karl DeisserothStanford neuroscientist and psychologist who led the new study, has been interested in the heart’s role in emotional processing since early in his career, when he learned as a psychiatry resident that an increased heart rate is a symptom common in panic disorders.
It is now well established that tachycardia, the term for an increased heart rate, is a hallmark of anxiety in mice and humans. But until now, there was no way to directly test whether an increased heart rate could induce an emotional response, he explains.
It will be decades before Deisseroth develops the tools to do so. About fifteen years before the new study was published, he and his lab discovered light-sensitive proteins called channelrhodopsins and developed optogenetics, a method of turning neurons on or off with light that has since revolutionized neuroscience. But these early light-sensitive proteins weren’t sensitive enough for researchers to noninvasively stimulate large organs like the heart. This is partly because most of the visual light spectrum does not penetrate the skin much beyond a few millimeters. Red light passes a little better, but not enough to activate these first opsins.
Fluorescent image showing the expression of DAPI (blue) and ChRmin (red) in a mouse heart.
In 2019, as they continued to explore opsins with new properties, Deisseroth’s group discovered a new channelrhodopsin which is very sensitive to red light and conducts powerful electric currents. With the newly designed protein, which they called ChRmine, the researchers were finally able to manipulate cells deep in the body, including those in the heart.
In the new study, Deisseroth’s lab used a viral delivery strategy to create mice that express ChRmin in cardiomyocytes: electrically active heart cells that initiate contractions.
To induce tachycardia in these mice, Deisseroth and his colleagues fitted them with a small light vest of their own design, which acted as an optical pacemaker. When the vest turned on, it activated ChRmin-expressing cells in the mice’s hearts, temporarily increasing their heart rate, which normally sits at around 600 beats per minute, up to 900 beats per minute.
Before that, “it was impossible to directly, causally, and accurately test” the hypothesis that heart rate influences emotional states, Deisseroth says. The scientist. “It was just exciting to be able to do that.”
But simply increasing the mice’s heart rate didn’t seem to affect their behavior – they didn’t show signs of anxiety, such as avoiding places where they had consistently high heart rates. This discovery surprised Deisseroth at first,” who explains that “when our heart rate goes up, it’s very often when things are aversive.”
However, things changed when the researchers placed the mice in potentially risky situations. In one experiment, for example, researchers replaced the closed cages the mice are normally housed in with large open environments known to stress them out. “An exposed environment is very aversive for mice because their main concern is to be [preyed upon]says Deisseroth. In these environments, mice expressing ChRmin exhibited more anxious behavior than normal mice after light stimulation. They avoided the center of the arena, choosing to huddle around its edges. “If the brain perceives a potentially threatening environment, then [the heart going faster] causes anxiety-related behavior,” notes Deisseroth.
“It shows very elegantly that context is needed to assess cues or experience as anxiety,” says Garfinkel. In humans, an increase in heart rate can be due to excitement, restlessness or fear, depending on the context. This is also true in mice: the brain must assess the environment to attribute an emotion to a physiological response, speculates Garfinkel.
Deisseroth and his colleagues then identified the parts of the brain to which the heart talks. By fluorescently labeling a marker of brain activity, a gene called fosthe researchers isolated two regions of the brain: the posterior insular cortex, a region of the brain that receives information from the body’s internal organs, and the prefrontal cortex, which receives information from the heart.
Finally, the researchers wanted to establish a causal link between heart rate and brain activity, which meant doing optogenetics on the brain and heart simultaneously. “It was quite a remarkable experience,” says Deisseroth. Using optogenetics, the researchers turned off cells in the posterior insular cortex and prefrontal cortex in some mice while stimulating the heart. When they silenced the posterior insular cortex (but not the prefrontal cortex), elevated heart rate no longer increased anxious behaviors in stressful situations. ” This does not mean [the prefrontal cortex] is not involved one way or another. He clearly receives the information that the heart is beating faster. . . but perhaps it uses this information on longer time scales.
Garfinkel says the findings could potentially inform work on anxiety and post-traumatic stress disorder. “I’d like to see what happens in animals with PTSD,” she says, “because based on my human work, I suspect traumatized animals don’t show the moderation of this effect based on their context.” She would also like to learn more about individual differences between how different humans and animals respond to an increased heart rate, which could also shed light on how anxiety disorders are treated.
Deisseroth says these findings show that heart rate targeting could be a good therapeutic avenue for panic disorders. “In people who have elevated heart rate and anxiety disorders, heart rate modulation can and perhaps should be a treatment goal in itself,” he says. Many cardiac procedures “are safe and well tolerated. It could help people a lot. »