Why do we need sleep?

In the new Japanese laboratory, an international team of scientists is trying to figure out what makes us fall asleep

Tsukuba , Japan. Outside the International Institute of Joint Medicine, the air is filled with the heavy and sweet smell of osmanthus , and the big golden spiders spin their webs in the bushes. Two people in helmets quietly talking, measuring the area of ​​the blue-gray walls near the entrance and putting glue on them. The building is so new that even the signs did not have time to hang on it.

The institute is only five years old, the building itself is even smaller, but more than 120 researchers from such different fields as pulmonology and chemistry, and from different countries, from Switzerland to China, have already gathered in it. One hour north of Tokyo, at the University of Tsukuba, with funding from the Japanese government and other sources, the Institute’s director, Masashi Yanagisawa, created a space to learn the basics of sleep biology — which differs in more common subjects of study, like causes of sleep problems and methods of their treatment. It is full of rooms with sparkling equipment, quiet chambers in which mice sleep, and spacious workplaces united by a spiral staircase. Here, enormous resources are concentrated on studying why living organisms actually need sleep.

Ask researchers this question and hear how feelings of awe and disappointment creep into their voices. It's amazing how universal is the dream: in the midst of feverish battles for survival, in all eras of bloodshed, death, escapes, countless millions of living creatures lay down to be unconscious for some time. It does not look like a suitable way to spend a full life fight. “This is crazy, but this is the case,” says Tarja Porkka-Heiskanen from the University of Helsinki, a leading somnolog biologist. The fact that such a risky habit is so widespread and constant suggests that the processes going on during sleep should be extremely important. What the dream gives to the asleep is worth it again and again to tempt death throughout life.

The exact benefits of sleep are still a mystery, and this bias is fascinating to many biologists. One rainy evening in Tsukuba, a group of institute scientists gathered at the Izakaya Bar, fails to mention a dream for only the first half hour of intercourse. Even the simplest jellyfish has to rest longer if you make it more awake than usual - one of the scientists surprisingly reports, quoting a new work describing an experiment in which these small creatures were periodically pushed by streams of water. And pigeons - did you read the work about pigeons? - asks another scientists. All researchers agree that something amazing happens in a dream. On the table, vegetables and tempura cool, forgotten in the face of amazing mysteries.

In particular, it is this need to fill the lack of sleep, which was observed not only in jellyfish and people, but also in all representatives of the animal world, scientists are trying to use to solve the problem of the need for sleep in general. The need for a dream is considered by many to be the key to understanding what it gives us.

Biologists call this need "sleep pressure": if you do not go to bed for too long, the pressure increases. Feel sleepy in the evenings? Naturally - you have not slept all day, and injected sleep pressure. But, like “dark matter”, this name describes something that we do not understand the nature of. The more you think about sleep pressure, the more it resembles the Tolkien puzzle game: what grows when you are awake and dissipates in a dream? Is this a timer? Molecule that grows during the day and needs to be removed? What is this metaphorical clock counting, hidden in some part of the brain, waiting until it is cleared at night?

In other words, asks Yanagisawa, who reflects on this in his personal, sun-drenched office of the Institute: “What is the physical basis of drowsiness?”

Biological studies of sleep pressure began more than a hundred years ago. In some of the most famous experiments, the French scientist kept dogs from sleeping for ten days. Then he pumped fluid from their brain and injected it into the brain of well-rested dogs, which instantly sank into sleep. This fluid contained something that accumulated during lack of sleep, which made the dogs fall asleep. So began the hunt for this ingredient - an assistant to Morpheus, with a finger on the light switch. Obviously, the discovery of this hypnotoxin, as the French researcher called it, should have revealed the secret of why animals tend to sleep.

In the first half of the 20th century, other researchers began attaching electrodes to the scalp of people, trying to look at the sleeping brain through the skull. Using electroencephalograms (EEG), they found that in a dream the brain does not turn off at all, but works according to a certain pattern. After the eyes close and breathing becomes deeper, the dense and feverish melting of the electric waves of the EEG shifts and turns into unusually long, pulsating waves of early sleep. After 35-40 minutes, metabolism slows down, breathing levels off, and it is not so easy to wake the sleeper. After some time, the brain switches and the waves become short and dense again: this is the rapid eye phase [REM] in which we see dreams. One of the first researchers at REM discovered that, by observing eye movements over the eyelids, he could predict when the baby would wake up — such a trick had hit the mothers. People repeat this cycle over and over again, waking up at the end of the REM phase, with a memory filled with winged fishes and melodies that they cannot recall.

Sleep pressure changes these brain waves. The more the subject was not allowed to sleep, the greater will be the waves during the slow sleep phase preceding REM. This phenomenon was observed in almost all living beings, which were supplied with electrodes and kept awake for too long - in birds, sea lions, cats, hamsters and dolphins.



If you need more proof that a dream, with its strange multi-stage structure and a tendency to fill your consciousness with any nonsense, is not just some passive state that saves energy, then you should know that the Syrian hamsters observed the following feature: they woke up from hibernation, to sleep. What they received as a result of sleep is not available to them during hibernation. Even in spite of the fact that it slows down almost all the processes in their bodies, sleep pressure still accumulates. “I want to know why this particular brain activity is so important?” Says Casper Vogt, one of the researchers gathered at the new institute in Tsukuba. He shows on his screen, where data on the triggering of neurons in sleeping mice are visible. “What is so important to risk being eaten, not to eat yourself, to postpone reproduction - to leave everything for the sake of it?”

The search for hypnotoxin can not be called unsuccessful. Several substances have demonstrated a clear ability to induce sleep - including the adenosine molecule, which accumulates in certain parts of the brain of awake mice, and disappears during sleep. Adenosine is especially interesting in that, apparently, it is the adenosine receptors that caffeine acts on. When he contacts them, adenosine cannot do this anymore - this is how the invigorating property of coffee works. But work on hypnotoxins does not fully explain how the body tracks sleep pressure.

For example, if adenosine puts us to sleep at the moment of transition from wakefulness to sleep, where does it come from? “No one knows,” observes Michael Lazarus, a researcher at the institute who studies adenosine. Some say that from neurons, some - that this is another class of brain cells. But there is no agreement. In any case, “the question is not in storage,” says Yanagisawa. In other words, these substances themselves do not store information about sleep pressure. They represent only a reaction to it.

Sleep-inducing substances may appear in the process of creating new connections between neurons. Chiara Chirelli and Giulio Tononi, sleep researchers at the University of Wisconsin, suggest that because our brain builds these connections while awake, it is possible that during sleep it removes unnecessary connections, eliminates memories or images that are inconsistent with others, or useless in terms of knowledge of the world. “Sleep is a good way for the brain to get rid of memories,” says Tononi. Another group of scientists discovered a protein that penetrates into little-used synapses and destroys them, and it does it in particular with a high level of adenosine. Perhaps this cleaning process occurs in a dream.

In this process, there are still many unknown quantities, and researchers are working on many other areas in an effort to get to the origins of sleep pressure and sleep. One group from Tsukuba University, under the direction of Yu Hayasi, destroys a certain group of cells in the brain of mice - and this procedure can lead to unexpected consequences. By preventing mice from experiencing REM sleep, shaking them just at the moment when they are going to enter it, causes a strong RR pressure that mice have to replenish in the next sleep cycle. Whether the mice suffer from this is another matter, but for now the team is exploring how fast sleep affects their abilities in cognitive tests. But it follows from the experiment that these cells, or certain sets of cells into which they enter, can keep in themselves records of sleep pressure, when it comes to watching dreams.

Yanagisawa was always inclined towards projects of an epic scope - for example, the massive study of thousands of proteins and cell receptors in order to understand their purpose. Such a project led him to study sleep about 20 years ago. They and their colleagues, opening a neurotransmitter , they called Orexin , realized that with his lack of mice faint because they fall asleep. It turned out that this neurotransmitter is not enough for people suffering from narcolepsy - they can not produce it. This idea helped bring about a real wave of research exploring this condition. A group of chemists from the University of Tsukuba is working together with a pharmacological company to investigate the potential of orexin-like substances for the treatment of this disease.

Currently, Yanagisawa and his colleagues are working on a large-scale, large-scale study of genes to identify genes associated with sleep. Project mice are injected with a substance that causes mutations. Then they are supplied with sensors for EEG, and when they go to bed on a bed of sawdust, the machines record their brain waves. Today, scientists have analyzed sleep for more than 8,000 mice.

When a mouse sleeps somehow incorrectly - often wakes up, or sleeps too long - researchers begin to delve into its genome. If they find a mutation that can cause this effect, they try to create a mouse with such a mutation and study the issue of sleep interruption. Over the years, many successful scientists have conducted similar research on animals such as fruit flies, and achieve impressive results. But the advantage of using mice, although such experiments compared to experiments on the front sights, is very expensive, is that you can connect the EEG electrodes to the mice, just like a person.

Several years ago, this group of scientists discovered a mouse that could not get rid of sleep pressure. Her EEG showed that she lives in a state of constant exhausting sleepiness. The same symptoms were also demonstrated by mice with such a mutation created specially. “This mutant of sleepy waves with a large amplitude was more than usual, it was constantly in a sleepy state,” says Yanagisawa. Mutation occurred in the SIK3 gene. The more the mutants did not sleep, the more protein gained chemical labels SIK3. Researchers published their discovery of SIK3 in the journal Nature in 2016.

It is still not entirely clear how SIK3 is associated with drowsiness, but the fact that the label accumulates on the enzyme like sand grains on the bottom of an hourglass is very interesting for researchers. “We are convinced that SIK3 is one of the central players in this field,” says Yanagisawa.

Researchers continue to wade in the mysterious darkness of drowsiness, and such discoveries illuminate their path like rays of lanterns. How they relate to each other, how they can come together and make a more general picture is unclear.

Researchers hope that the clarification will come - maybe not in a year, and not in two, but someday and earlier than one could imagine. Meanwhile, at the International Institute of United Medicine, mice do their work, wake up and fall asleep, in plastic trays, standing row by row. And in their brains, as in ours, lies a secret.