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.

We all know it can be hard to concentrate when you are sleep-deprived, but why does this happen? It may be because your brain is trying to refresh itself, causing momentary lapses in attention.

During sleep, the brain carries out a rinse cycle, where cerebrospinal fluid (CSF) is repeatedly flushed into the organ and out again at the base of the brain. This process clears out metabolic waste that has built up during the day – and that would otherwise damage brain cells.

at the Massachusetts Institute of Technology and her colleagues wondered whether lapses in attention, which commonly occur after sleep deprivation, may result from the brain trying to catch up on rinsing itself when it’s awake.

To explore this idea, the researchers asked 26 people aged between 19 and 40 to get a good night’s sleep that left them feeling well-rested, then kept them awake all night in a lab two weeks later.

In both cases, the team recorded the participants’ brain activity using MRI scans the next morning, while they completed two tasks. During these tests, participants had to push a button whenever they heard a specific tone or saw a cross on a screen turn into a square. This occurred dozens of times over 12 minutes.

As expected, the participants failed to press the button substantially more often when they were sleep-deprived compared with when they were well-rested, meaning a lack of sleep made it harder to focus.

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Crucially, when the researchers analysed the brain scans, they found that participants lost focus about 2 seconds before CSF was flushed out of the base of their brain. What’s more, CSF was drawn back into the brain about 1 second after attention recovered.

“If you think about the brain-cleaning process like a washing machine, you kind of need to put the water in and then slosh it around and then drain it out, and so we’re talking about the sloshing part occurring during these lapses of attention,” says Lewis.

The findings suggest that when the brain can’t clean itself during sleep, it does so when you’re awake, but this impairs concentration, says Lewis. “If you don’t have these waves [of fluid flowing] at night because you’re kept awake all night, then your brain starts to kind of sneak them in during the daytime, but they come with this cost of attention.”

Exactly why this cleaning process leads to a loss of attention remains unclear, but pinpointing the brain circuits that are responsible could reveal ways to reduce the cognitive effects of sleep deprivation, says Lewis.

Different people may experience one of five types of sleep, and these profiles each highlight how our shut-eye affects our health.

Previous research has found associations between sleep and ,  and physical conditions, such as . But these studies often looked at the relationship with just one aspect of sleep, such as its duration or quality.

To take a more holistic approach, at Concordia University in Montreal, Canada, and her colleagues analysed the association between seven factors related to sleep – such as sleep satisfaction and the use of sleeping aids – and 118 other measures, including cognition, substance use and mental health. They collected data including cognitive tests, sleep surveys and brain scans from 770 healthy adults aged between 22 and 36 in the US.

From this, the researchers identified five distinct sleep profiles. The first was characterised by a general pattern of poor sleep – greater sleep disturbances, decreased sleep satisfaction and taking a longer time to fall asleep – and worse mental health, such as depression and anxiety symptoms, as well as anger, fear and stress.

The brain scans of people in this group also showed decreased connectivity between networks involved in self-reflection, such as the temporoparietal network, and those responsible for attention and tasks, such as the somatomotor and dorsal attention networks. This could indicate disruptions in the brain’s ability to shift between the inner and outer world, according to the researchers. For instance, people in this category may ruminate on their thoughts and feelings, rather than focusing on their external environment.

People in the second sleep profile also showed signs of worse mental health, particularly related to inattention, but not sleep difficulties. Rather, they had decent sleep overall. “We have interpreted this as sleep resilience,” says Kebets. “So worse mental health, which doesn’t necessarily affect sleep.” People who fit this profile also lacked the brain connectivity patterns seen with the first group, which suggests these patterns are specifically related to sleep issues, rather than overall mental health.

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Meanwhile, the third profile exhibited a relationship between using sleep aids – such as prescription medication or even just teas marketed as helping sleep – and poorer memory and emotional recognition, which is the ability to identify someone’s emotional state through cues such as their expressions or body language. This could explain why people who fit this profile had decreased connectivity in brain regions involved with vision, memory and emotion.

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The fourth profile was distinguished by getting fewer than 7 hours of sleep a night, . This was associated with worse accuracy and longer reaction times on cognitive tests measuring emotional processing, language and social skills. This profile was also associated with more aggressive behaviours and increased connectivity across brain networks. Past studies of sleep deprivation have found , suggesting this is indicative of sleep debt.

Aggression also occurred in the fifth profile, which was characterised by sleep disturbances, such as waking multiple times a night. These disturbances were associated with worse language processing and working memory, as well as signs of poorer mental health, including anxiety symptoms and substance misuse.

These findings bring us closer towards understanding the complex relationship between sleep and health, says Kebets. “Sleep is so central to your sense of well-being, and it’s related to cognition, to physical health, to mental health, to substance use – so many aspects of your functioning.”

But not all of the participants fit neatly into one profile, says Kebets. The researchers also didn’t find evidence of causal relationships between sleep profiles and traits, only of associations. There will no doubt also be a significant proportion of people who regularly experience good-quality sleep. In addition, the participants were mostly white, so the study may have missed sleep profiles that exist among other ethnicities.

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