Why do we need a dream?

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

Tsukuba , Japan. Outside the International Institute for Combined Medicine, the air is filled with the heavy and sweet smell of osmanthus , and large golden spiders weave their cobwebs in the bushes. Two helmets spoke quietly, measuring the area of ​​the bluish-gray walls near the entrance and applying glue to them. The building is so new that even 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 diverse fields as pulmonology and chemistry, and from different countries, from Switzerland to China, have already gathered in it. An hour north of Tokyo, on the territory of Tsukuba University, funded by the Japanese government and other sources, the director of the institute, Masashi Yanagisawa, created a space for studying the basics of sleep biology - which differs from more common subjects, such as the causes of sleep problems and methods for their treatment. It is full of rooms with sparkling equipment, quiet chambers in which mice sleep, and spacious workplaces joined by a spiral staircase. Here, enormous resources are concentrated on the study of why, in fact, living organisms need sleep.

Ask researchers this question and listen to how feelings of awe and disappointment creep into their voice. It is amazing how universal the dream is: in the midst of feverish battles for survival, in all epochs of bloodshed, death, escapes, uncountable millions of living creatures lay down to stay unconscious for some time. It does not look like a suitable way to spend a full struggle life. “It's crazy, but this is how it is,” says Tarja Porkka-Heiskanen of the University of Helsinki, a leading somnologist. 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 sleep gives the sleeper is worth it, again and again, to tempt death throughout life.

The exact benefits of sleep are still a mystery, and many biologists are fascinated by this unknown. One rainy evening in Tsukuba, a group of scientists from the institute who gathered in the izakaya bar manage not to mention the dream for only the first half hour of communication. Even the simplest jellyfish have to rest longer if they are forced to stay awake more than usual - one of the scientists reported this in surprise, citing a new work describing an experiment in which these small creatures were periodically pushed with jets of water. And the pigeons - did you read the work about pigeons? - asks another scientist. All researchers agree that something amazing happens in a dream. On the table, vegetables and tempura cool, forgotten in the face of amazing puzzles.

In particular, it is this need to make up for 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. Many consider the need for sleep to be the key to understanding what it gives us.

Biologists call this need “sleepy pressure”: if you don’t go to bed too long, the pressure rises. Feel sleepy in the evenings? Naturally - you did not sleep all day and pumped up sleepy pressure. But, like "dark matter", this name describes something, the nature of which we do not yet understand. The more you think about sleepy pressure, the more it sounds like a puzzle game from Tolkien: what grows when you are awake and dissipates in a dream? Is that a timer? Molecule that grows during the day and requires removal? What kind of metaphorical counting of hours is hidden in some part of the brain, waiting until it is reset to zero at night?

In other words, Yanagisawa asks, reflecting on this in his personal, sunlit office of the institute: “What is the physical basis of sleepiness?”

Biological studies of carotid pressure began more than a hundred years ago. In some of the most famous experiments, the French scientist kept the dogs awake for ten days. Then he pumped liquid from their brain and injected it into the brain of well-rested dogs, which instantly fell into sleep. This liquid contained something that accumulated during sleep deprivation, which caused the dogs to fall asleep. So began the hunt for this ingredient - Morpheus's assistant, a finger on the light switch. Obviously, the discovery of this hypnotoxin, as the French researcher called it, was supposed to reveal 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 (EEGs), 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 the breathing becomes deeper, the dense and feverish flickering 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 is leveled, and it is not so easy to wake the sleeping person. After some time, the brain switches and the waves become short and dense again: this is the phase of REM [REM] in which we see dreams. One of the first REM researchers found that by observing eye movements over the centuries, he can predict when the baby wakes up - such a trick struck mothers. People repeat this cycle over and over again, waking up at the end of the REM phase, with a memory filled with winged fish and melodies that they cannot remember.

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



If you need more evidence that a dream, with its strange multi-stage structure and the tendency to fill your mind with all sorts of nonsense, is not just some kind of passive state that saves energy, then know that Syrian hamstersobserved 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 though it slows down almost all the processes in their bodies, sleepy pressure still builds up. “I want to know why exactly this 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 the data on the activation of neurons in sleeping mice is visible. “What is so important to risk being eaten, not to eat it yourself, to postpone reproduction - to give up everything for this?”

The search for hypnotoxin cannot be called unsuccessful. Several substances have demonstrated a clear ability to induce sleep - including the adenosine moleculeaccumulating in certain areas of the brain of awake mice, and disappearing during sleep. Adenosine is especially interesting in that, apparently, it is caffeine that acts on adenosine receptors. When he binds to them, adenosine does not succeed 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 euthanizes us at the moment of transition from wakefulness to sleep, where does it come from? “No one knows,” observes Michael Lazarus, an adenosine researcher at the institute. Some say that of neurons, some say that it is a different class of brain cells. But there is no agreement. In any case, “the issue is not storage,” says Yanagisawa. In other words, these substances themselves do not store information about sleep pressure. They represent only a reaction to it.

Sleep-causing substances may appear in the process of creating new connections between neurons. Chiara Cirelli and Giulio Tononi, sleep researchers from the University of Wisconsin, suggest that since our brain builds these connections while awake, it may remove unnecessary connections during sleep, eliminate memories or images that are inconsistent with others, or useless in terms of cognition of the world. “Sleep is a way for the brain to get rid of memories,” says Tononi. Another group of scientists discovered a protein that penetrates into poorly used synapses and destroys them, and he can do this, in particular, with a high level of adenosine. Perhaps this cleaning process occurs in a dream.

There are still many unknown quantities in this process, and researchers are exploring many other directions in an effort to get to the origins of sleep pressure and sleep. One group from the University of Tsukuba under the leadership of Yu Hayashi destroys a certain group of cells in the brain of mice - and this procedure can lead to unexpected consequences. Preventing mice from experiencing REM sleep, shaking them just at the moment they are about to enter it, causes intense REM sleep pressure, which mice have to make up in the next sleep cycle. Whether mice suffer from this is another question, but for now, the team is exploring how REM affects their abilities in cognitive tests. But from the experiment it follows that these cells, or some sets of cells into which they enter, can store in themselves records of sleeping pressure,

Yanagisawa has always been inclined to projects of epic proportions - for example, to mass research of thousands of proteins and cellular receptors in order to understand their purpose. It was such a project that led him to the study of sleep about 20 years ago. Having discovered a neurotransmitter , called orexin , they and colleagues realized that when it was deficient, the mice fainted because they were falling asleep. It turned out that this neurotransmitter is not enough for people suffering from narcolepsy - they cannot produce it. This idea helped trigger a real wave of research studying this condition. A team of chemists from the University of Tsukuba is working with a pharmaceutical company to study the potential of orexin-mimicking substances to treat this disease.

Currently, Yanagisawa and colleagues are working on a large-scale large-scale study of genes, designed to identify genes associated with sleep. Mice participating in the project are injected with a mutation inducing substance. Then they are equipped with sensors for EEG, and when they go to bed on a bed of sawdust, the machines record their brain waves. To date, scientists have analyzed the sleep of more than 8,000 mice.

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

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 drowsiness. Mice with such a mutation, specially created, also showed the same symptoms. “This mutant of large-amplitude sleepwaves was larger than usual, it was constantly in a sleepy state,” says Yanagisawa. The mutation occurred in the SIK3 gene. The more the mutants did not sleep, the more protein scored SIK3 chemical labels. 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 researchers were very interested in the fact that the label accumulates on the enzyme like grains of sand at the bottom of the hourglass. “We are convinced that SIK3 is one of the central players in this area,” says Yanagisawa.

Researchers continue to wade through the mysterious darkness of drowsiness, and such discoveries illuminate their path like the rays of lanterns. How they are connected with each other, how they can come together and make a more general picture is not yet clear.

Researchers hope that clarification will come - maybe not in a year, or in two, but sometime, and sooner than one could imagine. Meanwhile, at the International Institute of Combined Medicine, mice go about their business, wake up and fall asleep, in plastic trays, standing next to each other. And in their brains, as in ours, there is a secret.