Researchers have identified specific groups of neurons in the brains of mice that are activated after the rodents have been awake for a long time, driving them to get some sleep.��If a similar system exists in humans, it could be targeted to help improve treatments for some sleep disorders.

Inside the brain, several neural circuits , including neurons in the hypothalamus that .��

One or more of these circuits might be involved in why it is that, the longer we are awake, the more irresistible the urge to close our eyes becomes. But what actually drives this impulse has long been a mystery.

To find out,  at the University of Basel in Switzerland and his colleagues have compared brain activation patterns in mice during normal sleep-wake cycles, sleep deprivation and recovery sleep. They did this by tracing how much protein is produced in cells by a gene called����Dz�, which is turned on when neurons are in the process of activating.

“We saw that very specific parts of the brain were correlated with wakefulness,” says Joo. This allowed the researchers to identify areas in which activity correlated with time spent awake.��

Within one of these regions, the median raphe nucleus, they found two distinct neuronal populations that were increasingly activated the longer the animals stayed awake and that got quieter again after sleep started. These populations are the GABAergic and serotonergic neurons, so named because the chemical messenger molecules they respond to are gamma-aminobutyric acid (GABA) and serotonin, respectively.

“This is an outstanding study. The whole-brain Fos mapping is a real tour de force,” says  at the University of Wisconsin–Madison.

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To see whether these neuronal populations became more active simply because the mice had been awake for a long time or whether they do something more, Joo and his colleagues then used viruses to deliver a genetic package to the neurons to either activate or inhibit their action.

When both sets of neurons were artificially activated, the mice slept for twice or three times as long as control mice and spent more time in non-REM slow-wave sleep – in a way that resembles the deeper recovery sleep humans have after we have been up for a long time.��

“Not only does it increase the amount of time the animal spends sleeping, but it also increases the quality of the sleep,” says Joo.

When the neurons were inhibited, the mice slept about 70 per cent less than control mice – spending around 6.5 extra hours awake a day – without showing more of the anxiety-like behaviours that usually come with sleep deprivation for mice. However, the lack of sleep was lethal in about 17 per cent of the mice.��

The strong effect of activating and inhibiting the neurons means they don’t just signal that an animal has been awake, says team member , also at the University of Basel. “They are crucial to promote sleep, and may be key components of the neural circuitry that generates sleep drive.” 

The study “adds to a growing body of work showing that there are distinct sleep circuits that are activated by wakefulness, yet promote sleep”, says  at Johns Hopkins University in Maryland, whose research has shown that neurons in a brain region called the thalamic nucleus reuniens track the gap between how much sleep we need and how much we actually get.

It isn’t known if the same sleep-driving neuron populations exist in humans, but if they do, the findings could open doors to new therapies for some sleep-related conditions – once we know how the cells are communicating with other brain regions, say the researchers.��

Projections from these neurons in the median raphe nucleus , and these areas are known to work together to control the sleep-wake cycle.

“The effect of this major neuronal path on sleep is very strong, but, as we have learned since we started manipulating neuronal circuits, each path provides nuances. The brain has many ways to wake up and fall asleep,” says  at Stanford University in California.

For example, there are hints from experiments in fruit flies that mitochondria, which power cells, in the brain may play a crucial role in the onset of sleep.��

It may one day be possible to reap some of the benefits of sleep without ever closing our eyes. Stimulating specific brain activity in awake mice led to some of the same effects as deep sleep, including a boost in memory.

“It should be possible, at least in theory and to some extent, to replicate these results in our species,” says at the University of Oxford, who wasn’t involved in the research. “It would be fascinating to explore whether artificially inducing [this activity] during waking [hours] in humans can result in a subjective feeling of being more refreshed and rested afterwards.”

Sleep is thought to be an essential way for the brain to carry out most of its maintenance work. This includes synaptic homeostasis, the process whereby the brain declutters the thousands of new neural connections made during the day – storing important ones and weakening or cutting away ones that aren’t as necessary.

During non-rapid eye movement (NREM) sleep – the deep sleep state that makes up around 80 per cent of sleep in adults – the brain’s cortex repeatedly fires signals at the exact same time and then shuts those neurons off, in a pattern called slow-wave sleep activity. “This has been linked to synaptic homeostasis, and may be a key mechanism underlying sleep’s restorative functions,” says at the University of Wisconsin-Madison.

Cirelli and her colleagues wondered if a small part of the cortex could be nudged into entering this deep sleep state while an individual is still awake. Some animals do this naturally, such as dolphins, ducks and fur seals, in which one half of the brain enters NREM sleep while the other remains alert and vigilant for predators.

To see if a similar state could be induced, the researchers genetically engineered mice so their neuronal activity could be switched off using light. They implanted a probe into one half of their brain and kept the mice awake for five hours by giving them new things to explore. Near the end of this time period, the light probe was repeatedly turned on and off for 30 minutes, mimicking NREM sleep.

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Afterwards, when the mice were allowed to sleep, brain recordings showed that the stimulated side of the brain didn’t show the usual signs of exhaustion caused by sleep deprivation. “Because that small part of the brain did its decluttering while awake, it no longer needed extra deep sleep afterwards,” says Cirelli.

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Next, the researchers wondered whether forcing sleep during wakefulness boosts memory. So they placed the genetically modified mice in a square box with carpet that had the same texture on both sides of the container. After 15 minutes of exploring the space, the mice were assigned to either a sleep group, a group that was sleep-deprived for 1 hour, or a group that was sleep-deprived for 1 hour but received the artificial deep-sleep stimulation.

The next day, the mice went back into the box, but one side of the container had a new texture. Mice are naturally drawn to novelty, so the researchers measured how much they remembered the old environment by the amount of time they spent on the new side. They found that the sleep-deprived mice that received no stimulation seemed to struggle to tell the new and old side apart, while both the sleep group and the sleep-deprived mice that received the stimulation spent more time on the new side.

The team plans to study whether similar effects could come about in people if this brain activity were induced non-invasively via transcranial electrical stimulation. However, Vyazovskiy stresses that sleep can probably never be replaced. “Sleep is of two kinds – NREM and REM [rapid eye movement] – and we still do not know what it is about the alternation of these two states that makes sleep complete,” he says.