People were always thinking about sleep. The nature of sleep and the content of dreams attracted the attention of thinkers. It is impossible not to notice that the state of consciousness and body during sleep is very different from the state during wakefulness. Explanations for this phenomenon were very different, and in many cases the authors of ancient sleep theories were based on anthropological models that are poorly compatible with modern natural science. For example, the doctrine that the soul moves in a dream to an immaterial world, in which a person experiences a conscious experience, but without the participation of the body.

The most primitive natural-scientific concept of sleep interprets this state as follows: during the day, the brain is attacked by information from the outside, and at night, in darkness and silence, the brain receives a minimum of external stimuli, which changes the nature of its work. The brain goes into “sleep mode”. In this concept of sleep, the brain is a device that can be turned on or off, without variations in operating modes.

To explain why the brain “turns off”, a variety of theories were invented that emphasized one or another aspect of the body’s vital activity. Since the time of Ancient Rome, the theory linking the causes of sleep with the movement of blood in the vessels has been very popular. According to one version, the blood becomes too much, the brain is pressed against the bones of the skull and “turns off”. According to another version, on the contrary, there is an outflow of blood from the brain, the brain turns pale and “turns off”.

By the end of the nineteenth century, the influence of vascular theory had waned. Scientists agreed that blood circulation does change during sleep, but this can not be considered a reason for the onset of sleep. In the second half of the nineteenth century, another theory gained weight — sleep begins due to changes in nerve cells.

Since the beginning of the XX century, sleep is more often spoken about using the concepts of behavioral psychology. The key position in the new theory of sleep in the research of Academician Pavlov. For Pavlov, sleep is a state of inhibition that covers the entire brain. The inhibition phase is always present in the work of the nervous system, but at the end of the day or after prolonged stimulation of the brain by complex tasks, total inhibition occurs and the brain “turns off”. It sounds convincing, but Pavlov did not describe the physiology of the process. This was done for him by another Russian academician — Vladimir Bekhterev. Bekhterev believed that a person falls asleep when the reflex protection of the brain from poisoning by metabolic products that accumulate during the day is triggered.

Vascular, nervous, biochemical, and other theories of sleep were based on the understanding of sleep as a passive state of the brain. The passive concept of sleep was strengthened by observations of patients with lethargic encephalitis. It was a mysterious brain disease, presumably of viral origin, which for unknown reasons disappeared after the epidemic of the 1920s. Patients with lethargic encephalitis could sleep for several weeks at a time. After they were found to have defects in the regions of the brain responsible for logical operations, it was concluded that sleep occurs when the brain (logic analyzer) turns off. Active brain-wakefulness, passive brain-sleep.

Sleep research technologies, primarily the recording of brain wave activity using EEG, have refuted the passive theory of sleep in all its varieties. It turned out that the cerebral cortex does not “turn off” during sleep, but behaves very actively.

This discovery is associated with the beginning of the history of modern sleep science. In the 1950s, a link was found between the eye movements of a sleeping person and the wave activity of the brain. The phase of sleep in which the brain exhibits specific activity similar to that observed in a waking person is called the REM sleep phase, or REM-rapid eye movement (REM — rapid eye movement, meaning “rapid eye movements”) [45]. The study of REM sleep has helped advance the understanding of sleep as a physiological process.

Many have written about dreams. For Freud, this is the most important area of research, which he called ” the royal path to understanding the role of the unconscious in psychic life.” But virtually no one who has written about dreams has been able to explain how a particular concept of dreams can be used in the study of sleep physiology. The development of the EEG and the discovery of REM sleep made it possible to look at the dream from the outside, fixing objective parameters, without relying solely on the subjective experience of the dreamer.

The discovery of REM sleep dealt a blow to the position of behaviorists, who believed that those who want to study the psyche, only the study of behavior is available. The science of living things is limited to observable behavior, so there is no point in arguing about subjective experience. However, in the state of REM sleep, the brain is active, despite the fact that no behavior is observed.

Another equally important phase of sleep is slow sleep, or non-REM sleep (from the English non-rapid eye movement, i.e. the phase of sleep without rapid eye movements). In the slow phase, the brain changes the pattern of its work: neurons begin to work synchronously (in wakefulness, they each work in their own rhythm), and the activating centers begin to gradually subside until complete silence. It is believed that it is in this phase that the most important processes of brain recovery and its purification from metabolites accumulated during the day occur.

Medicine has always lagged behind basic sleep research. By the beginning of the twentieth century, a huge number of texts on sleep and dreams had accumulated, but from a medical point of view, only two conditions were systematically described: narcolepsy [46] and sleeping sickness.

The description of narcolepsy in 1880 was the first step towards the creation of a clinical discipline dealing with sleep disorders. Prior to this, a condition now known as obstructive sleep apnea syndrome was described. However, the description was given not by a doctor, but by the writer Charles Dickens. In “The Pickwick Club Notes” there is a character suffering from daytime sleepiness and excess weight. The cause of daytime sleepiness in his case was apnea.

At all times, the most common sleep disorder was insomnia. Surprisingly, the purposeful study of insomnia began later than narcolepsy and snoring. In the XIX century, it was fought with the help of drugs, mainly bromine compounds were used, which served as a universal sedative. Then the bromine was replaced by barbiturates. Their effectiveness explains a certain slowdown in the development of the science of insomnia. Insomnia was not seen as a condition that should be treated in the same way as other diseases are treated. Insomnia was treated as a symptom of other diseases, which is eliminated by suitable sleeping pills. Sleep disorders were attributed to diseases of the body and neurasthenia, or otherwise associated with anxiety and hypersensitivity.

A huge amount of intellectual resources were spent on Freudian research in the field of sleep. Psychoanalysis has fascinated everyone with the idea that what a sleeping person experiences is a symbolic representation of something that the analyst must reveal. Sleep as a psychophysiological process, and dreams themselves are relegated to the background in psychoanalysis. The semiotics of dreams is studied, which is fascinating and useful in its own way, but gives little information for the natural-scientific analysis of sleep.

Freud was right when he spoke about the importance of dreams and how they provide unique information about the human psyche, especially about the emotional sphere. The problem is how Freud proposed to work with dreams. The psychoanalytic interpretation of dreams catastrophically subjective and unsubstantiated from the scientific point of view. There is no doubt that dreams can reveal our desires. But it is unlikely that the analysis of these desires always needs to refer to the concept of “unconscious”. In addition, dreams manifest not only desires, but also fears — a fact that Freud was never able to explain.

Allan Hobson, founder of the Laboratory for the Neurophysiology of dreams, compared Freud’s hypotheses with the ideas adopted in modern neuroscience:

1) Explanation of the trigger mechanism of dreams

Freud: The release of unrealized desires.

Neurobiology: Activation of certain areas of the brain during sleep (see below).

2) Explanation of the features of dreams

a) Quirkiness

Freud: The disguise and censorship of subconscious desires.

Neurobiology: Chaotic, ascending (from bottom to top, from older brain structures to newer ones) activation process; activation of the inferior parietal cortex and deactivation of the dorsolateral prefrontal cortex.

b) Strong emotions.

Freud: I couldn’t explain!

Neurobiology: Selective activity of anterior limbic structures: amygdala, anterior cingulate cortex, parahippocampal cortex, hippocampus, and medial frontal regions.

c) Amnesia

Freud: Repression.

Neurobiology: Aminergic demodulation, which means a sharp decrease in the processes of memory fixation.

d) Hallucinations

Freud: Regression to the sensory level.

Neurobiology: Activation of REM sleep waves — high-frequency low-amplitude waves. For example, activation of the basal ganglia, cerebellum, primary motor and sensory cortex, the signal from which is blocked at the level of the trunk and spinal cord, leads to the appearance of fictitious movements in sleep and sensorimotor hallucinations, and activation of the associative visual cortex leads to visual hallucinations.

e) Delusions, loss of reflexive consciousness

Freud: The dissolution of the ego.

Neurobiology: Selective deactivation of the dorsolateral prefrontal cortex.

3) the Functions of dreaming

Freud: The “Sentinel” of sleep.

Neuroscience: Dreaming is an epiphenomenon that most often occurs in the REM phase. It is important to remember that the REM sleep phase, which has become “popular” in science because of its association with dreams, is evolutionarily more archaic than the slow sleep phase. The proportion of REM sleep increases in more advanced mammals and is completely absent in cold-blooded animals.

In the 1960s, doctors began to pay more attention to the connection of insomnia with mental disorders, especially depression. It is difficult to ignore the obvious range of causes and consequences: a painful state of mind disrupts sleep, and disturbed sleep worsens mental health.

Belatedly, in the 1970s and 1980s, medicine is developing a new theory of sleep disorders, in which insomnia is studied as a separate problem. The ICD-11 has its own category for sleep disorders, outside of psychiatric and other diagnostic groups.

Current research has shown that sleep disorders are associated with increased blood concentrations of inflammatory markers (such as C-reactive protein and interleukin-6, which are predictors of depression). Moreover, significant deviations in sleep duration (less than 6 hours or more than 8 hours per night) lead to an increase in the level of systemic inflammation. This immune activation in response to sleep disorders is most pronounced in young women, i.e. in the group with the highest risk of depression.

Moreover, sleep disorders and depression intersect with severe somatic diseases that have an inflammatory basis — asthma, rheumatoid arthritis and cardiovascular diseases. It is in such cases that it is permissible to talk about psychosomatics, and not when the biological explanation of the disease for some reason seems unconvincing.

Neuroimaging techniques have helped to better understand the fundamental neurobiology of sleep. A simplified scheme for the transition from wakefulness to sleep looks like this: during wakefulness, the monoamine system inhibits GABA neurons, which become active during sleep and in turn suppress monoamine neurons.

The monoamine system is activated by impulses from hypothalamic neurons that synthesize the neuropeptide orexin [49]. The latter receive excitatory signals from neurons of the limbic system, the suprachiasmal nucleus (the “Main clock” of the brain), as well as hypothalamic structures that analyze and regulate energy balance. It follows that wakefulness depends on the emotional state (limbic system), circadian rhythms (suprachiasmal nucleus) and the energy level of the body. Of the above, circadian rhythms are most strongly influenced by genetics and biology. For the discovery of the molecular mechanisms of circadian rhythms, scientists from the United States Jeffrey Hall, Michael Rosbash and Michael Young were awarded the Nobel Prize in 2017.

The history of this discovery began in 1880, when Charles Darwin and his son Francis made a suggestion about the hereditary nature of circadian rhythms, which was confirmed by experiments with crossing different varieties of beans, whose circadian rhythms differed from each other. In hybrids, the period length was different from the period length of both parents. The endogenous nature of circadian rhythms was finally confirmed in 1984 during experiments with fungi of the species Neurosporacrassa (Neurosporacrassa), conducted in space. These experiments showed the independence of circadian rhythms from geophysical signals associated with the rotation of the Earth around its axis. Exactly how the internal circadian biological clock works has long been a mystery.

In 1970. Seymour Benzer and his student Ronald Konopka were looking for genes that control the circadian rhythm in fruit flies. They demonstrated that the flies ‘ circadian clock is disrupted by mutations of an unknown gene. This unknown gene is called the period — Per gene. But how does this gene affect the circadian rhythm?

The 2017 Nobel laureates, who also studied fruit flies, decided to answer this question. In 1984, Jeffrey Hall and Michael Rosbash were able to isolate the period gene. They then found that PER, a protein encoded by the period gene, accumulates during the night and degrades during the day. Thus, PER protein levels fluctuate over a 24-hour cycle, in sync with the circadian rhythm.

The chronology of events during the 24-hour cycle is as follows. When the period gene is active, the corresponding mRNA is synthesized. mRNA is transferred to the cytoplasm of the cell and serves as a matrix for PER protein synthesis. The PER protein accumulates in the cell nucleus, exerting a blocking effect on the period gene. This triggers the negative feedback inhibitory mechanism that underlies the circadian rhythm.

In the following years, other molecular components of this mechanism were elucidated, explaining its stability and functioning. Species-specific genes, additional proteins needed to activate the Per gene, and the mechanism by which light synchronizes the cycle were identified.

The biological clock is involved in many aspects of our complex physiology. We now know that all multicellular organisms, including humans, use a similar mechanism to control circadian rhythms. Most of our genes are regulated by the biological clock, and therefore a carefully calibrated circadian rhythm adapts our physiology to different stages of the day. The circadian clock anticipates and adapts physiological processes to a specific time of day. The biological clock helps regulate sleep, nutrition, hormone synthesis, blood pressure, and body temperature.

The study of circadian rhythm is important for understanding many diseases, including mental ones. Among them, urinary incontinence associated with a violation of the cyclic production of vasopressin, affective disorders, which by their dynamics and clinic reflect susceptibility to circadian rhythms, various sleep disorders, and many others. Circadian biology has become a vast and dynamic field of research, which can not but have a beneficial effect on our health and well-being.