Same neurons at work in sleep and under anesthesia

Anesthesiologists aren’t totally lying when they say they’re going to put you to sleep. Some anesthetics directly tap into sleep-promoting neurons in the brain, a study in mice reveals.

The results may help clarify how drugs that have been used around the world for decades actually put someone under. “It’s kind of shocking that after 170 years, we still don’t understand why they work,” says study coauthor Max Kelz of the University of Pennsylvania in Philadelphia.

Most neurons in the brain appear to be calmed by anesthetics, says neuropharmacologist and anesthesiologist Hugh Hemmings Jr. of Weill Cornell Medical College in New York City. But the new results, published online October 25 in Current Biology, show that two common anesthetics actually stimulate sleep-inducing neurons. “It’s unusual for neurons to be excited by anesthetics,” Hemmings says.

In the study, Kelz, Jason Moore, also of the University of Pennsylvania, and colleagues studied the effects of the anesthetics isoflurane and halothane. Mice given the drugs soon became sleepy, as expected. Along with this drowsiness came a jump in nerve cell activity in a part of the brain’s hypothalamus called the ventrolateral preoptic nucleus, or VLPO.

Not all neurons in the VLPO are the same. Some are involved in kicking off sleep, while neighboring neurons don’t seem to play a role. The anesthetics affected only the VLPO neurons that promote sleep, Moore and his colleagues found. When the scientists destroyed VLPO neurons, the mice were less sensitive to the effects of isoflurane. These animals needed higher doses of the drug to make them groggy, suggesting that this particular spot in the brain is important for anesthetic effects.

The drugs in the study aren’t commonly used in the United States but share similarities with anesthetics that are. There’s some evidence that propofol, the anesthetic that Michael Jackson co-opted as a sleep aid, may activate the same population of sleep-inducing neurons, says Kelz.

Even after finding this direct link between natural sleep and being under anesthesia, Kelz says it’s clear that the two situations are different. “Despite what we tell our patients, anesthesia and sleep are not at all the same,” he says. “They are really distinct states.” 

But understanding how the brain turns off — as it does each night during sleep or under anesthesia — may lead to a clearer view of some of the deepest mysteries about the brain, such as how the brain generates consciousness.

And the finding could help scientists design better anesthetics. “The drugs that we have are fraught with side effects that we’d like to eliminate or avoid,” Hemmings says. Studies like this one, which clarify how the brain responds to anesthesia, will point out which brain changes are important and which are side effects, he says. “It’s hard to have designer drugs without knowing what they’re designed to do.”