Scientists locate the part of the brain where sighs are made

Your life depends on your ability to sigh.

Yes, we sigh when we’re exhausted or stressed -- and when the weight of the world feels like too much to bear -- but it turns out that sighing is also an essential life-sustaining reflex that is necessary to keep our lungs from collapsing.

This week researchers from UCLA and Stanford University describe the neural circuitry of sighing for the first time as well as pinpoint the exact location in the brain from which our sighs originate.

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The study, published Monday in Nature, could lead to treatments for people who don’t sigh enough, or those who sigh too much, the scientists said. It could also offer clues to how sighs might be triggered by emotional states.

Chances are you sigh much more than you realize. Most humans heave an involuntary sigh an average of 12 times an hour, said Jack Feldman, a professor of neurobiology at UCLA and a senior author on the paper.

You can test this for yourself by lying down in a quiet room and paying close attention to your breathing. About once every five minutes you will notice that your body takes an inhalation, and just before the exhale, adds another inhalation on top of it.

These types of sighs are not related to emotion, Feldman said. Instead, they provide an extra gust of air that helps to re-inflate some of the 500 million tiny balloon-like sacs in our lungs called alveoli.

The alveoli are the site where oxygen enters the blood stream and carbon dioxide is removed. Although each individual sack is just 2/10th of a millimeter in diameter, together they have the surface area of a tennis court.

When they collapse, the only way to pop them open again is to sigh, which brings in twice the volume of a normal breath, Feldman said.

And we’re not the only animals who sigh regularly. Rodents are even more frequent sighers than humans, taking a double inhale about 25 to 40 times an hour.

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The discovery of how the brain turns a normal breath into a sigh originated from two separate lines of inquiry from Feldman’s lab at UCLA and biochemist Mark Krasnow’s lab at Stanford.

About eight years ago, Feldman’s colleague at UCLA Wiktor Janczewski discovered he could get a rat to sigh up to 400 times an hour if he injected a molecule called bombesin into the lower part of its brain stem. This part of the brain, called the pre-Bötzinger complex, is well known as the core of the breathing control center of the body.

Bombesin is a toxin found on the skin of South American frogs, but mammal neurons produce molecules similar to bombesin as well.

Janczewski launched on his experiments after reading that rodents produce bombesin-related molecules, or peptides, when they are stressed and that they, and humans, sigh more when stressed. His work showed that bombesin can control sighing in the pre-Bötzinger complex.

Several years later, Kevin Yackle, a student in the lab of Mark Krasnow, professor of biochemistry at Stanford, was investigating what molecules are highly expressed in regions of the brain associated with breathing. After screening more than 19,000 gene expression patterns in animals, he found two small populations of neurons that produce bombesin-related molecules in a region of the brain close to the pre-Bötzinger complex.

The two labs then worked together to show that the cells Yackle identified were indeed the ones that produced the molecules that excite neurons in the pre-Bötzinger complex to control the sigh rate in mice.

“What we did is discover the location of the cells that produce the peptides, the projection of these peptides to the pre-Bötzinger complex, and the cells that have the receptors for these peptides,” Feldman said.

The new work could help scientists develop drugs that can induce sighing in people who don’t naturally sigh enough, or be used to inhibit sighs in those who suffer anxiety and other psychological disorders that can lead to too much sighing.

The researchers might also look to see if emotional centers located in higher regions of the brain also produce bombesin-related peptides that trigger sighing when we’re feeling stressed out or unhappy.

“While we have a good handle on the physiological reasons we sigh, it’s still a mystery what function or functions it plays during emotional states,” Feldman said.

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