One of the main questions that have worried physiologists since the time of I.P. Pavlov is the existence of a “sleep center” in the brain. Direct study of neurons involved in the regulation of sleep-wakefulness has shown that the normal functioning of the thalamus- the cortical system of the brain, which provides the entire range of conscious human activity in wakefulness, is possible only in the presence of powerful influences from structures called activating. Due to these influences, the membrane of a significant majority of cortical neurons in wakefulness is depolarized, and only in this state of depolarization are these neurons able to process and respond to signals coming to them from other nerve cells. There are probably five or six such brain activation systems (they can be conventionally called “centers of wakefulness”), and they are localized at all cerebral levels: in the reticular formation of the trunk, in the region of the blue spot and dorsal nuclei of the suture, in the posterior hypothalamus and basal nuclei of the anterior brain. In humans, a violation of the activity of any of these systems cannot be compensated for at the expense of others, is incompatible with consciousness and leads to a coma.
It seemed logical to assume that if the brain has “centers of wakefulness,” then there must be “centers of sleep.” However, a detailed study of neurons has shown that positive feedback mechanisms are built into the system for maintaining wakefulness, in the form of special neurons whose function is to inhibit activating neurons, and which are themselves inhibited by these neurons. These neurons are scattered in different parts of the brain, although their accumulation is noted in the reticular part of the substantia nigra; they have in common the release of the same chemical mediator – gamma-aminobutyric acid, the main inhibitory substance of the brain. As soon as the activating neurons weaken their activity, the inhibitory neurons turn on and weaken it even more. The process develops downward for some time, until a certain “trigger” is triggered and the entire system is thrown into another state – wakefulness or paradoxical sleep. A reflection of this process is a change in patterns in the electrical activity of the brain during the 90-minute sleep cycle of a person.
Another evolutionarily ancient brain inhibitory system uses adenosine as a mediator.
The most important role of prostaglandin D2 synthesized in the brain in modulation of adenosinergic neurons was shown . Taking into account the fact that all brain prostaglandin synthase -D is contained in the meninges and choroid plexus, the role of this system in the formation of hypersomnia becomes obvious (in traumatic brain injury, meningitis, African “sleeping sickness”, etc. ).
It has been shown in experiments on laboratory animals that, as sleep deepens, more and more powerful inhibitory postsynaptic potentials dominate, alternating with periods of activation, of the “burst-pause” type. Under these conditions, the ability to process information in the brain worsens. Discharges of neural activating systems are progressively reduced . Thus, during slow sleep, cerebral homeostasis is restored and other restorative processes, for example, the synthesis of phosphatergic compounds (“energy storage”), growth hormone (somatotropic hormone), proteins and nucleic acids. From this point of view, wakefulness and slow sleep are like “two sides of the same coin.” The absence of a single “center of slow wave sleep” (taking into account its importance) makes the system of its organization more reliable, not entirely dependent on the activities of one center in the event of any disturbances in its functioning. At the same time, long-term total suppression of NREM is impossible, since it must periodically replace wakefulness, and under conditions of artificial suppression of sleep, the brain goes to various tricks, just to preserve the representation of NREM sleep. It is also important that in conditions of slow sleep, the processing of information by the brain does not stop, but changes: from processing exteroceptive (external) the brain goes on to processing interoceptive (internal) impulses. Thus, the function of slow wave sleep includes not only recovery processes, but also the optimization of the management of internal organs.
Unlike slow sleep, REM (paradoxical) sleep is triggered from a specific center located in the back of the brain, in the region of the pons and medulla oblongata. The mediators of these cells are acetylcholine, glutamic and aspartic acids. During REM sleep, brain cells are active, but information from the senses (afferent) is not supplied to them, and the descending (efferent) is not supplied to the muscular system. This is the paradoxical nature of this state. At the same time, the information that was received in the previous wakefulness and is stored in memory is intensively processed; in addition, the formation of a future program of behavior takes place in REM sleep. Inadequate inclusions of the “paradoxical sleep center” do indeed occur in some rather rare types of genetically determined pathology (narcolepsy, etc.). Unlike wakefulness, in REM sleep, only activating systems, localized in the reticular formation of the trunk, function and use acetylcholine, glutamic and aspartic acids as transmitters . All other activating systems are turned off, and their neurons are inactive for the entire period of paradoxical sleep. This silence of a significant number of activating systems of the brain is the fundamental fact that determines the difference between wakefulness and paradoxical sleep at the physiological level.
Traditionally discussed neurochemical agents that play a role in the sleep-wake cycle.
- NREM sleep phase: GABA, serotonin
- NREM sleep phase: norepinephrine, acetylcholine, glutamate
- Wakefulness: norepinephrine, glutamate, acetylcholine, histamine, serotonin
New neurochemical agents that play a role in the organization of the sleep-wake cycle.
- orexin / hypocretin
- delta sleep inducing peptide
- interleukins, muramylpeptide , cytokines
- prostaglandins (PGD2)