You wake up, stretching sweetly in a soft bed, get up and see through the huge window the sun rising over the ocean, the white sand of the beach and palm trees. A fresh sea breeze is blowing through the open door of the loggia and the sound of the surf is heard. You drink aromatic freshly ground coffee, leave the doors of a two-storey villa, get into the car with a rearing horse on the hood, turn the key and to the noble roar of the V8 engine … You finally wake up from the ringing of the alarm clock.
Again, the insidious brain made us believe in the reality of what was happening. But how does he do it? How does one manage to make a person lie almost motionless for seven or more hours, while showing the most interesting blockbusters with an exciting plot? The reason for this is the most complex biochemical processes, in which not one or two brain structures are involved, but a whole network. How does the interaction and "switching" of wakefulness to sleep occur? How does sleep develop and when do dreams come? Why sometimes, waking up from the alarm clock, we feel capable of moving mountains, and sometimes irritatedly ready to destroy everything around?
Through the veil of time
Somnology - the science that studies sleep - appeared relatively recently, because the age of the first fundamental research in the "kingdom of Morpheus" does not exceed 120 years. Prior to that, sleep was given a mystical meaning as a borderline state between life and death. Aristotle said: "Sleep, apparently, belongs by its nature to such states as, for example, the borderline between life and not life, and the sleeping person does not exist completely, and does exist." The great physician of antiquity, Hippocrates, believed that sleep occurs as a result of the outflow of blood and heat from the head into the internal regions of the body. This explanation dominated the minds of European scientists and was taken on faith for almost two thousand years. In one thing, Hippocrates was right: the reasons for a person's immersion in the world of dreams had to be sought in the head.
The sleep regulation network functions as a trigger with no intermediate positions. This mechanism is possible due to the interlocking of the centers of falling asleep and awakening. As soon as one of the parties gains an advantage, the entire system instantly goes into the opposite state. So that she does not switch back and forth every minute, orexin stimulates all centers of wakefulness, without suppressing the center of sleep. This slight imbalance makes it difficult to switch just enough that we relatively rarely transition from sleep to wakefulness and vice versa. For the transition to sleep, it is necessary that the excitation system weakened, and the activity of the sleep center increased. This slow process is familiar to everyone as gradually increasing fatigue.
And now the twentieth century has come. In Germany, a patient is admitted to the clinic of Professor Strumpel, who has partially lost his sight and hearing as a result of trauma - deaf in one ear and blind in one eye. Doctors noticed that when both remaining "windows to the world" were closed, the patient fell asleep. The famous physiologist Pavlov became interested in these observations and decided to conduct similar experiments on his favorite subjects - dogs. He found that if you exclude the constant influx of impulses from the senses into the cerebral cortex, then sleep occurs. The scientist also investigated the effects of monotonous stimuli, repeatedly repeating light touches to the skin of the thigh of the hind paw. They almost always euthanized animals, and this gave the researcher the right to believe that sleep is a conditional inhibition that spread widely across the cerebral cortex,which is designed to protect the dog's brain from excessive repetitions of any irritation.
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The next step towards overcoming the secrets of sleep was the emergence of the electroencephalography (EEG) method. In 1905, the German physiologist Hans Berger for the first time registered sinusoidal oscillations of electric potential with a frequency of 8-11 Hz in a person who was in a calm state with closed eyes, most pronounced in the occipital regions of the brain. These fluctuations are called the alpha rhythm.
The onset and duration of sleep are regulated by complex physiological processes, among which there are two main ones - the homeostatic need for sleep (the so-called process S, down arrows) and the internal clock (process C, up arrows in the figure). The yellow line shows the "sum" of these two processes.
In the 1930s, the situation became a little clearer: scientists, having cut the cat's brain stem at the midbrain level, caused the animal to have a coma - a state similar to sleep. At the same time, slow electrical oscillations were observed on the cat's EEG, which were later called "sleepy spindles" (the drawing resembled a spindle turned upside down). When the brain was cut at the level of the first cervical segments, separating the spinal cord from the brain, it was possible to obtain the so-called preparation of the waking brain: the cat followed the objects moving in front of it with its eyes, and the EEG showed oscillations with a frequency of 14-30 Hz (beta rhythm). It became clear that in the brain of animals there are different structures - responsible for falling asleep and responsible for awakening.
Center of cheerfulness
At the end of the 19th century, Vladimir Bekhterev and Santiago Ramon y Cajal described the structures of the cat's brain stem responsible for the state of wakefulness, who saw an open cluster of neurons, penetrated by nerve fibers, in the middle of the brain stem. But why this formation is needed, the Italian neuroscientist Giuseppe Moruzzi and the American neurologist Horace Magun established only in the second half of the twentieth century. They called this structure the reticular formation ("reticula" in Latin means "network"). It is in the brain stem that the nuclei are located, which concentrate in themselves all the impulses from sensory receptors going to the brain. Long processes (axons) of neurons of the reticular formation are connected to the cerebral cortex and to the neurons of the spinal cord. Nerve fibers from the cortex and from the spinal cord also go to the reticular formation itself,so a complex feedback system is formed. Signals from the reticular formation (reticular discharge) trigger the mechanisms of wakefulness in the cerebral cortex, and the cortex, in turn, controls the state of the reticular formation.
Casket with sleep
In 1990, the film Awakening was released, based on the book of the same name by the famous psychiatrist Oliver Sachs. He talks about a strange group of 80 elderly patients who have been suffering from an unknown disease resembling autism or Parkinson's for more than 40 years. Sachs' patients were the last surviving victims of a mysterious epidemic that suddenly began in Europe in the winter of 1916-1917, then spread throughout the world and killed 5 million people in the period after the First World War. The patients fell into sudden apathy and suffered from high fever, visual impairment and hallucinations. Then the disease turned into a chronic form and was accompanied by a huge number of various clinical manifestations. But all forms had one thing in common - sleep disorder. This fact seemed interesting to the Viennese neurologist Baron Konstantin von Economo. He found that some patients slept too much, for weeks, months, waking up only to drink and eat, while others completely lost sleep. At autopsies, the scientist found a similar anatomical picture: in a certain area of the diencephalon in patients, there was a massive death of nerve cells.
This area of the brain is called the hypothalamus because it is located under the thalamus, the area of the brain that redistributes signals from the senses. If we could insert the index finger directly into the head at the level of the bridge of the nose, then we would have rested exactly in the hole where it is located - the "Turkish saddle". The hypothalamus is one of the most important centers that control the autonomic nervous system, regulating, in particular, body temperature, blood pressure, appetite, sexual desire and thirst. Economo, of course, did not know all this. However, he suspected that there must be a center that controls sleep. “Apparently, - concluded the researcher, - these cells do something, thanks to which we fall asleep.”
Now, thanks to the research of Clifford Seiper from Harvard University in Boston, it became known that in the hypothalamus there really is a special area that is activated when falling asleep - the ventrolateral preoptic region (VLPO). The axons of neurons from the VLPO go down to the areas that support wakefulness. Conversely, in order to prevent us from falling asleep, the center of vigor needs to have a connection with the hypothalamus, so that the nerve fibers go from the bottom up.
Seiper and his colleagues concluded that the cells in the anterior part of the hypothalamus are the sleep center, which uses their axons to suppress the wakefulness centers in the brainstem, which includes the midbrain and pons. This process ultimately leads to falling asleep. “Perhaps this is the key to the entire mechanism that, through the hypothalamus, controls the state of sleep and wakefulness,” the neurologist wrote. So in 2005, the modern concept of sleep appeared, which Siper published in his article in the journal Nature. According to this concept, the entire "sleep system" is a network of several interconnected nodes that switch in a special way at certain points in time and regulate sleep and wakefulness.
Brain confrontation
The first part of the general sleep-wake system is the inhibitory system. This is VLPO in the anterior hypothalamus, from which an inhibition wave is sent to the wakefulness system, and this leads to the transfer of the brain into a "sleep mode". From the point of view of biochemistry, the main "brake fluid" of the system is gamma-aminobutyric acid (GABA). By acting on special receptors, it suppresses the activity of neurons. GABA receptors are a channel in the cell membrane surrounded by large protein molecules that can change their spatial structure (relatively speaking, "unfold" or "fold"). When GABA binds to receptors, the channel lumen increases, more chlorine ions pass through it, which leads to a decrease in the electrical conductivity of the cell membrane - making it less sensitive to electrical influences. And this leads to the suppression of impulse activity - the cell "reduces the speed" from a quick "gallop" to a calm "step".
The second part of the system is the excitation system, which is based on eight nerve nodes that form two parallel bundles. Through them, excitation waves are conducted to the cerebral cortex. One bundle begins in the reticular formation (this is the brainstem), the other in the so-called blue spot (Locus coeruleus). The cells here produce most of the excitatory neurotransmitter norepinephrine in the brain. The area is responsible for the occurrence of fear and panic, as well as for a large part of our arousal.
There are other neurotransmitters (dopamine, serotonin, and others), but they are associated with different processes in the brain. However, there is another specific sleep neurotransmitter. The lateral (lateral) hypothalamus contains several tens of thousands of nerve cells that produce a special neurotransmitter, orexin (hypocretin). Biochemists isolated this substance only in 1998. If there is too little orexin or if the brain lacks the corresponding receptor molecules, a rare disease occurs - narcolepsy, which is characterized by sudden bouts of sleepiness and falling asleep.
Day, night - day away
However, this is only part of the mechanism of sleep. Like all living nature, people live in accordance with their own internal rhythms, which are tied to the cycles of day and night. There is a time when a person is prone to sleep, and there is a time for active work. The body has a "biological clock" - the melatonergic system. The main players in it are the suprachiasmal nuclei of the hypothalamus and the pineal gland (pineal gland), which are located in the intermediate region of the brain.
When light hits the retina, information about this goes to the suprachiasmatic nuclei of the hypothalamus (small hours), and then, having traveled a long way, it enters the pineal gland, or the so-called third eye, which serves many animals, for example, reptiles and birds. light level detector. In humans, in the process of evolution, the large hemispheres of the brain have significantly increased, closing the pineal gland, and he has lost contact with light. Nature had to "invent" all this complex and existing nowadays way of regulating the synthesis of "sleepy" hormone.
The pineal gland produces melatonin, the hormone of night and darkness. When the light levels drop in the evening, melatonin is released, which signals the cells to “end the day”. Its main function is the inhibitory effect on the suprachiasmatic nuclei, through which the wakefulness systems are activated.
This process can be compared to the operation of a thermostat that maintains a certain temperature in the refrigerator. The longer we live an active life, the more forcefully the sleep center feels the urge to flip the switch to sleep. The longer we sleep, the less the need for sleep, so that at some point the wakefulness system takes over and we wake up and feel like we have slept. This model of regulation is called two-factor, and it was developed in 1982 by the head of the Department of Psychopharmacology and Somnology at the University of Zurich, Alexander Borbeli. According to her, our need for sleep at a certain point in time is the result of the interaction of chronobiological and homeostatic (maintaining internal balance) factors. The scientist called these components process S and process C. Process S is the homeostatic component of the need for sleep, and process C is the influence of the internal clock, the main task of which is to leave the night for long sleep.
"Process S, by contrast, is like an hourglass," says Borbeli. - During wakefulness, the sand is poured from above into the lower vessel; when falling asleep, the clock is turned over. Therefore, for a feeling of good rest, it is important not only how much time we slept in a row, but also how much time we spent during the day to form the S component. And this has a good practical application, known to many: if you know that in the next you will not be able to get enough sleep at night, you can try to sleep early in the middle of the previous day. And then you will feel much better.
And this is just a cursory glance at the system responsible for sleep. As Jürgen Zulli, a somnologist from Regensburg, says, "Sleep is not rest, it is a different wakefulness."
Anna Horuzhaya