A new study published in the journal Nature has pinpointed two tiny clusters of neurons in the brain stem that are responsible for transforming normal breaths into sighs.

Sighing appears to be regulated by the fewest number of neurons we have seen linked to a fundamental human behavior," explained the author. "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."

"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."

Using a mouse model, researchers screened more than 19,000 gene-expression patterns in the animals' brain cells. They found roughly 200 neurons in the brain stem that manufacture and release one of two neuropeptides, which enable brain cells to talk to each other. Still, the scientists did not know which brain cells these neurons communicated with or why.

They discovered that the peptides triggered a second set of 200 neurons. These cells activate the mouse's breathing muscles to produce a sigh -- roughly 40 times an hour.

The researchers found that blocking one of the peptides cut the animals' sighing rate in half. Silencing both peptides halted the mice's ability to sigh completely.

"These molecular pathways are critical regulators of sighing, and define the core of a sigh-control circuit," author said. "It may now be possible to find drugs that target these pathways to control sighing."

Sighing is vital to lung function, and thus to life, author emphasized. On average, a person sighs every five minutes, which translates into 12 sighs per hour. The purpose of sighing is to inflate the alveoli, the half-billion, tiny, delicate, balloon-like sacs in the lungs where oxygen enters and carbon dioxide leaves the bloodstream. Sometimes, though, individual sacs collapse.

Turning on sighing would be useful in people who cannot breathe deeply on their own. Early artificial breathing devices did not regularly give patients a deep breath, and many patients died. Current ventilators regularly deliver a large inflation of air that mimics a sigh.

"If you don't sigh every five minutes of so, the alveoli will slowly collapse, causing lung failure," author said. "That's why patients in early iron lungs had such problems, because they never sighed."

The ability to limit the sighing reflex could prove useful in anxiety disorders and other psychiatric conditions where sighing grows debilitating. The mechanism behind the emotional roots of conscious sighing remains a mystery.

https://www.uclahealth.org/news/ucla-and-stanford-researchers-pinpoint-origin-of-sighing-reflex-in-the-brain