In mice, neurons found to build sleep pressure

After a sleepless night, the urge to sleep can feel like a force that keeps rising by the hour. In mice, researchers at the Biozentrum of the University of Basel have identified brainstem neurons that do more than record time spent awake: they help create the pressure to sleep.

The team, led by Professor Alex Schier and working with Beth Israel Deaconess Medical Center and Auburn University, compared brain activity during normal sleep and wake cycles, sleep deprivation, and recovery sleep. It singled out two populations: GABAergic neurons, which use the inhibitory chemical messenger GABA, and serotonergic neurons, which use serotonin. Both became increasingly active the longer the mice remained awake, then quieted after sleep began.

The researchers tested whether the cells were merely a biological clock for wakefulness or an active part of the sleep response. Artificially activating both populations made the mice sleep longer and more deeply, producing a form of recovery sleep normally seen after prolonged wakefulness. Inhibiting the neurons had the opposite effect: the animals slept less and maintained alert wakefulness.

The most striking result came from sustained inhibition. The mice slept approximately 70% less than usual, and most did not display some of the severe behavioral impairments that typically accompany sleep deprivation. That finding suggests these neurons influence not only how much the animals sleep, but also how strongly sleep pressure accumulates over time.

So what changes, concretely? Scientists now have a way to manipulate a defined part of the circuit that makes sleep increasingly difficult to resist, opening experiments on sleep loss and possible sleep disorders. But the result is a mouse study, published in Nature; it does not yet show that the same circuit can be targeted safely or effectively in people. Future work will examine how these neurons connect with the rest of the brain and how they generate sleep drive at the molecular level.