A sleep switch

Activating the cells across the cortex of freely moving mice increased slow-wave and REM sleep, cut the time taken to fall asleep, and sent the animals into their nests during the day. Then the team tried it during the dark phase, when nocturnal mice are mostly awake.

“We could have them sleep more during the time that they are awake than they usually sleep during the day,” Batista-Brito said. “I never thought this experiment was going to work. We are manipulating one percent of inhibitory neurons with local injections, so we are hitting only a fraction of those cells. And we could see an effect that was really quite striking.”

That effect, Batista-Brito argues, points toward the idea that these neurons might be the cortex’s sensors of sleep pressure, something first proposed by Thomas Kilduff, the director of the SRI International’s Center for Neuroscience and co-author of the study.

Sleep, Batista-Brito explains comes in two flavors: the circadian sort that follows the light and homeostatic sleep, the accumulated fatigue that eventually makes us sleep whether we want to or not. Kilduff, Batista-Brito said, showed that after sleep deprivation, these are the most active cells in the cortex.

One question Batist-Brito and her colleagues still don’t have the answer to, though, is what activates these cells.

What flips the switch?

“One caveat of our work is that it was done in the visual cortex,” Batista-Brito said.

The findings about the coordinating role of the Sst-Chodl neurons, the team claims, should generalize to different brain regions, but the actual wiring may not. Batista-Brito’s lab is now repeating the anatomy part of their work in the prefrontal cortex. Their prediction is that there we’ll see inputs from other areas, such as the hypothalamus and the thalamus, and that will be what triggers the network for sleep specifically.

The cells are conserved from salamanders to humans, which is why the paper argues they could be an entry point into the sleep disruption running through so many psychiatric illnesses.

The team is now focused on three remaining questions: what activates these cells, whether they actually sense sleep pressure, and why they drive delta power.

Nature, 2026. DOI: 10.1038/s41586-026-10876-y