What Chill Mice Can Teach Us About Keeping Calm

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For generations, mothers have encouraged children to take long, slow breaths to fight anxiety. A long tradition of meditation likewise uses controlled breathing to induce tranquillity.

Now scientists at Stanford University may have uncovered for the first time why taking deep breaths can be so calming. The research, on a tiny group of neurons deep within the brains of mice, also underscores just how intricate and pervasive the links are within our body between breathing, thinking, behaving and feeling.

Breathing is one of the body’s most essential and elastic processes. Our breaths occur constantly and rhythmically, much like our hearts’ steady beating. But while we generally cannot change our hearts’ rhythm by choice, we can alter how we breathe, in some cases consciously, as in holding our breath, or with little volition, such as sighing, gasping or yawning.

But how the mind and body regulate breathing and vice versa at the cellular level has remained largely mysterious. More than 25 years ago, researchers at the University of California at Los Angeles first discovered a small bundle of about 3,000 interlinked neurons inside the brainstems of animals, including people, that seem to control most aspects of breathing. They dubbed these neurons the breathing pacemaker.

In the years since, though, little progress had been made in understanding precisely how those cells work.

But recently, a group of scientists at Stanford and other universities, including some of the U.C.L.A. researchers, began using sophisticated new genetics techniques to study individual neurons in the pacemaker. By microscopically tracking different proteins produced by the genes in each cell, the scientists could group the neurons into “types.”

They eventually identified about 65 different types of neurons in the pacemaker, each presumably with a unique responsibility for regulating some aspect of breathing.

The scientists confirmed that idea in a remarkable study published last year in Nature, in which they bred mice with a single type of pacemaker cell that could be disabled. When they injected the animals with a virus that killed only those cells, the mice stopped sighing, the researchers discovered. Mice, like people, normally sigh every few minutes, even if we and they are unaware of doing so. Without instructions from these cells, the sighing stopped.

But that study, while literally breathtaking, raised new questions about the capabilities of other neurons in the pacemaker.

So for the newest study, which was published recently in Science, the researchers carefully disabled yet another type of breathing-related neuron in mice. Afterward, the animals at first seemed unchanged. They sighed, yawned and otherwise breathed just as before.

But when the mice were placed in unfamiliar cages, which normally would incite jittery exploring and lots of nervous sniffing — a form of rapid breathing — the animals instead sat serenely grooming themselves.

“They were, for mice, remarkably chill,” says Dr. Mark Krasnow, a professor of biochemistry at Stanford who oversaw the research.

To better understand why, the researchers next looked at brain tissue from the mice to determine whether and how the disabled neurons might connect to other parts of the brain.

It turned out that the particular neurons in question showed direct biological links to a portion of the brain that is known to be involved in arousal. This area sends signals to multiple other parts of the brain that, together, direct us to wake up, be alert and, sometimes, become anxious or frantic.

In the mellow mice, this area of the brain remained quiet.

“What we think was going on” was that the disabled neurons normally would detect activity in other neurons within the pacemaker that regulate rapid breathing and sniffing, says Dr. Kevin Yackle, now a faculty fellow at the University of California, San Francisco, who, as a graduate researcher at Stanford, led the study.

The disabled neurons would then alert the brain that something potentially worrisome was going on with the mouse since it was sniffing, and the brain should start ramping up the machinery of worry and panic. In that way, a few tentative sniffs could result in a state of anxiety that, in a rapid feedback loop, would make the animal sniff more and become increasingly anxious.

Or, without that mechanism, it would remain tranquil, a mouse of Zen.

The implication of this work, both Dr. Krasnow and Dr. Yackle say, is that taking deep breaths is calming because it does not activate the neurons that communicate with the brain’s arousal center.

Whether deep breathing has its own, separate set of regulatory neurons and whether those neurons talk to parts of the brain involved in soothing and pacifying the body is still unknown, although the scientists plan to continue studying the activity of each of the subtypes of neurons within the pacemaker. This area of research is in its infancy, Dr. Yackle says.

It also so far involves mice rather than people, although we are known to have breathing pacemakers that closely resemble those in rodents.

But even if preliminary, this research bolsters an ancient axiom, Dr. Krasnow says. “Mothers were probably right all along,” he says, “when they told us to stop and take a deep breath when we got upset.”