Your life depends on your ability to sigh. Yes, we sigh when we're exhausted or stressed, but it turns out that sighing is also an essential life-sustaining reflex that is necessary to keep our lungs functioning properly.

Researchers from the University of California-Los Angeles and Stanford University recently described the neural circuitry of sighing for the first time and pinpointed the exact location in the brain from which sighs originate. They found two tiny clusters of neurons in the brain stem that are responsible for transforming normal breaths into sighs. The discovery may lead physicians to treat patients who cannot breathe deeply on their own — or who suffer from breathing disorders.

The study, published this past week in Nature, could also offer clues to how sighs might be triggered by emotional states.

“Sighing appears to be regulated by the fewest number of neurons we have seen linked to a fundamental human behavior,” Jack Feldman, a professor of neurobiology at UCLA and a senior author on the paper, said in an article posted on UCLA's website. “One of the holy grails in neuroscience is figuring out how the brain controls behavior. Our finding gives us insights into mechanisms that may underlie much more complex behaviors.”

People sigh much more than they realize. Most humans heave an involuntary sigh an average of 12 times an hour, said Feldman. These types of sighs are not related to emotion, Feldman said. Instead, they provide an extra gust of air that helps to reinflate the alveoli, the roughly 500 million balloon-like sacs in the lungs. The alveoli are the site where oxygen enters the bloodstream and where carbon dioxide is removed. And although each individual sac is just two-tenths 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.

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.

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 UCLA colleague Wiktor Janczewski discovered he could get a rat to sigh up to 400 times an hour if he injected the substance bombesin into the lower part of its brain stem, called the pre-Botzinger complex, which is 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.

Janczewski launched 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-Botzinger complex.

Several years later, Kevin Yackle, a student in Krasnow's lab, was investigating which 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-Botzinger 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-Botzinger 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-Botzinger complex, and the cells that have the receptors for these peptides,” Feldman said.

The new work could help scientists develop drugs to induce sighing in people who don't naturally sigh enough, or to inhibit sighs in those who suffer anxiety and other psychological disorders that can cause too much sighing. The researchers may explore if emotional centers in higher regions of the brain also produce bombesin-related peptides that trigger sighing associated with stress or sadness.