Good news for hopeless romantics and the perpetually dismayed: All that sighing is good for you. In fact, you’d die without it. Scientists have now pinpointed the region in the brain that transforms normal breathing into a life-giving sigh. They published their findings this week in the journal Nature

Let’s start with the mechanics. Physiologically speaking, sighing is a way of keeping your lungs inflated. “A sigh is a deep breath, but not a voluntary deep breath,” study co-author Jack Feldman said in a press release. “It starts out as a normal breath, but before you exhale, you take a second breath on top of it.” Whether you realize it or not, you do this about 12 times an hour, and even more than that when you’re stressed or anxious.

And it’s a good thing you do. “If you don’t sigh every five minutes of so, the alveoli will slowly collapse, causing lung failure,” Feldman said. “That’s why patients in early iron lungs had such problems, because they never sighed.” The machines had not been programmed to give patients regular deep, lung-filling breaths.

One group of researchers sifted through nearly 19,000 gene expression patterns in the active brains of mice, looking for the root of the sigh reflex. It was much smaller than they expected: just one little bundle of 200 cells in the brain stem, releasing one of two molecules called peptides. They shared their data with Feldman’s lab, and together the team found another set of 200 cells on the peptide receiving end.

A mouse's sigh clusters. Image credit: Stanford/Krasnow Lab

When the scientists prevented one peptide from reaching its goal, the rate of the mice’s sighing was cut in half. Blocking both peptides caused the mice to stop sighing altogether. 

“Unlike a pacemaker that regulates only how fast we breathe, the brain’s breathing center also controls the type of breath we take,” co-author Mark Krasnow noted in the press release. “It’s made up of small numbers of different kinds of neurons. Each functions like a button that turns on a different type of breath. One button programs regular breaths, another sighs, and the others could be for yawns, sniffs, coughs, and maybe even laughs and cries.”

It’s highly unusual for such small clusters of neurons to have so much power, Feldman said. “Sighing appears to be regulated by the fewest number of neurons we have seen linked to a fundamental human behavior.” 

The team’s findings may someday lead to treatment for people with diseases that limit their breathing. “These molecular pathways are critical regulators of sighing, and define the core of a sigh-control circuit,” Krasnow said. “It may now be possible to find drugs that target these pathways to control sighing.”