Mediators and modulators of the nervous system. Synapses and mediators of the central nervous system

According to the chemical structure, mediators are a heterogeneous group. It includes choline ester (acetylcholine); a group of monoamines, including catecholamines (dopamine, norepinephrine and epinephrine); indoles (serotonin) and imidazoles (histamine); acidic (glutamate and aspartate) and basic (GABA and glycine) amino acids; purines (adenosine, ATP) and peptides (enkephalins, endorphins, substance P). This group also includes substances that cannot be classified as true neurotransmitters - steroids, eicosanoids and a number of ROS, primarily NO.

A number of criteria are used to decide on the neurotransmitter nature of a compound. The main ones are listed below.

1. The substance must accumulate in presynaptic endings and be released in response to an incoming impulse. The presynaptic region must contain the system for the synthesis of this substance, and the postsynaptic zone must detect a specific receptor for this compound.
2. When the presynaptic region is stimulated, Ca-dependent release (by exocytosis) of this compound into the intersynaptic cleft, proportional to the strength of the stimulus, should occur.
3. Mandatory identity of the effects of the endogenous neurotransmitter and the putative mediator when it is applied to the target cell and the possibility of pharmacological blocking of the effects of the putative mediator.
4. The presence of a reuptake system of the putative mediator into presynaptic terminals and/or into neighboring astroglial cells. There may be cases when not the mediator itself, but the product of its cleavage is subjected to reuptake (for example, choline after the cleavage of acetylcholine by the enzyme acetylcholinesterase).

Influence of drugs on various stages of mediator function in synaptic transmission

	Modifying Influence	Result impact
Synthesis mediator	Precursor addition Reuptake blockade Blockade of synthesis enzymes	↓ ↓
Accumulation	Inhibition of uptake in vesicles Inhibition of binding in vesicles
Selection (exocytosis)	Stimulation of inhibitory autoreceptors Blockade of autoreceptors Violation of the mechanisms of exocytosis	↓ ↓
Action	Effects of agonists on receptors
on receptors	Blockade of postsynaptic receptors
Destruction mediator	Reuptake blockade by neurons and/or glia Inhibition of destruction in neurons
	Inhibition of destruction in the synaptic cleft

The use of various methods for testing the mediator function, including the most modern ones (immunohistochemical, recombinant DNA, etc.), is difficult due to the limited availability of most individual synapses, as well as due to the limited set of targeted pharmacological agents.

An attempt to define the concept of "mediators" encounters a number of difficulties, since in recent decades the list of substances that perform the same signaling function in the nervous system as classical mediators, but differ from them in chemical nature, synthesis pathways, receptors, has significantly expanded. First of all, the above applies to a large group of neuropeptides, as well as to ROS, and primarily to nitric oxide (nitroxide, NO), for which the mediator properties are well described. Unlike the "classical" mediators, neuropeptides, as a rule, are larger, are synthesized at a low rate, accumulate in low concentrations, and bind to receptors with low specific affinity; in addition, they do not have presynaptic terminal reuptake mechanisms. The duration of the effect of neuropeptides and mediators also varies significantly. As for nitroxide, despite its participation in intercellular interaction, according to a number of criteria, it can be attributed not to mediators, but to secondary messengers.

Initially, it was thought that a nerve ending could contain only one neurotransmitter. To date, the possibility of the presence in the terminal of several mediators released jointly in response to an impulse and acting on one target cell - concomitant (coexisting) mediators (commediators, cotransmitters) has been shown. In this case, the accumulation of different mediators occurs in the same presynaptic region, but in different vesicles. Examples of mediators are classical neurotransmitters and neuropeptides, which differ in the place of synthesis and, as a rule, are localized in one end. The release of cotransmitters occurs in response to a series of excitatory potentials of a certain frequency.

In modern neurochemistry, in addition to neurotransmitters, substances are isolated that modulate their effects - neuromodulators. Their action is tonic in nature and longer in time than the action of mediators. These substances can have not only neuronal (synaptic) but also glial origin and are not necessarily mediated by nerve impulses. Unlike a neurotransmitter, a modulator acts not only on the postsynaptic membrane, but also on other parts of the neuron, including intracellularly.

There are pre- and postsynaptic modulation. The concept of "neuromodulator" is broader than the concept of "neurotransmitter". In some cases, the mediator may also be a modulator. For example, norepinephrine, released from the sympathetic nerve ending, acts as a neurotransmitter on a1 receptors, but as a neuromodulator on a2 adrenergic receptors; in the latter case, it mediates inhibition of the subsequent secretion of norepinephrine.

Substances that perform mediator functions differ not only in their chemical structure, but also in which compartments of the nerve cell they are synthesized. Classical small molecule mediators are synthesized in the axon terminal and are incorporated into small synaptic vesicles (50 nm in diameter) for storage and release. NO is also synthesized in the terminal, but since it cannot be packaged in vesicles, it immediately diffuses out of the nerve ending and affects the target. Peptide neurotransmitters are synthesized in the central part of the neuron (perikaryon), packed into large vesicles with a dense center (100-200 nm in diameter) and transported by axonal current to the nerve endings.

Acetylcholine and catecholamines are synthesized from circulating precursors, while amino acid mediators and peptides are ultimately formed from glucose. As is known, neurons (like other cells of higher animals and humans) cannot synthesize tryptophan. Therefore, the first step leading to the beginning of the synthesis of serotonin is the facilitated transport of tryptophan from the blood to the brain. This amino acid, like other neutral amino acids (phenylalanine, leucine and methionine), is transported from the blood to the brain by special carriers belonging to the family of monocarboxylic acid carriers. Thus, one of the important factors determining the level of serotonin in serotonergic neurons is the relative amount of tryptophan in food compared to other neutral amino acids. For example, volunteers who were fed a low-protein diet for one day and then given a tryptophan-free amino acid mixture showed aggressive behavior and altered sleep-wake cycles associated with decreased levels of serotonin in the brain.

Picks(transmitters) - physiologically active substances that directly transmit information from one cell to another through special intercellular contacts - synapses.

On the periphery, two substances most often serve as mediators - ACh (neuromuscular synapses and synapses of the parasympathetic division of the ANS) and NA (synapses of the postganglionic fibers of the sympathetic division of the ANS). But in the CNS, excitation and inhibition can be transmitted from neuron to neuron with the help of many mediators. The most common excitatory mediators are glutamate, ACh, NA, D, serotonin, and the inhibitory ones are GABA and glycine. But there are also quite rare chemical messengers produced in a relatively small number of nerve cells. It is believed that mediators in our brain are at least 35-40 different substances. It is violations in the production or utilization of mediators that are the main cause of many nervous and mental disorders.

The properties of a substance capable of becoming a mediator are shown in Fig. 9.4.

Rice. 9.4.

1 - the mediator and its chemical precursors must be present in the neuron; 2 - the mediator must be contained in high concentrations in synaptic vesicles; 3 - the synaptic ending and (or) the body of the neuron must contain an enzymatic system for the synthesis of the mediator; 4 - the neurotransmitter should be released from the vesicles into the synaptic cleft when AP arrives at the nerve ending; 5 - the release of the mediator into the synaptic cleft during stimulation should be preceded by the entrance to the end of calcium ions; 6 - in the synaptic cleft, there must be a system for the degradation of the neurotransmitter and (or) a system for its reuptake into the presynaptic ending; 7 - on the postsynaptic membrane there must be receptors for the neurotransmitter

In its own way chemical nature mediators can be divided into " classical", which are modified amino acids, and " non-classical"- peptide and gaseous (Table 9.1). Traditionally, IA and D mediators, synthesized in the body from the dietary amino acid phenylalanine, which contains a catechol core, are called catecholamines. Serotonin, which is synthesized from the amino acid tryptophan and is an indole derivative by its chemical nature, together with NA and D, belongs to the group of biogenic amines, although there are many “amines” among other mediators.

Table 9.1

Some mediators found in animals

According to their effects, classical mediators are divided into excitatory and inhibitory. Much later than the "classical" mediators, peptide mediators were discovered, which are small chains of amino acids. The mediator role of several peptides has been proven, and several dozen peptides are “under suspicion”. And finally, rather unexpected was the discovery of the ability of cells to produce a number of gaseous substances, the secretion of which does not require "packaging" in vesicles; nevertheless they are full-fledged mediators. Better than other gases as a mediator, nitric oxide (NO) is known, but the mediator properties of CO and H 2 S are also beyond doubt.

Any mediator, regardless of chemical or physical nature, has its own life cycle, which includes the following steps:

• - synthesis;
• - transport to the presynaptic ending;
• - accumulation in vesicles;
• - release into the synaptic cleft;
• - interaction with the receptor on the postsynaptic membrane;
• - destruction in the synaptic cleft;
• - transport of the resulting metabolites back to the presynaptic ending.

The synthesis of mediators can occur both in the body of the neuron and in the presynaptic endings themselves. Molecules of mediators of a peptide nature are enzymatically "cut out" from large precursor proteins that are synthesized in the body of a neuron on a rough ER. Then these

mediators are packed in the Golgi apparatus into large vesicles, which, with the help of axonal transport, move along the axon to the synapses. "Classic" neurotransmitters are synthesized at the very end, where enzymes for the synthesis and packaging of molecules into vesicles come through axonal transport. In most neurons, one mediator dominates, but in recent years it has been established that several mediators can be present in the same neuron and, moreover, in the same synapse. They can be located both in the same and in different vesicles. Such coexistence has been shown, for example, for biogenic amines and peptide mediators.

The release of the mediator into the synaptic cleft occurs at the moment when the AP reaches the nerve terminal and the presynaptic membrane depolarizes (Fig. 9.5).

Rice. 9.5.

• 1 - PD in the iresynaptic fiber, leading to partial depolarization of the nerve ending; 2 - Ca 2+ in the extracellular space; 3 - Ca 2+ channel that opens when the membrane is depolarized; 4 - vesicles with mediator;
• 5 - the vesicle interacts with Ca 2+ and is embedded in the presynaptic membrane, ejecting the mediator into the synaptic cleft; 6 - the vesicle interacts with Ca 2+ and forms a short-term contact with the non-resynaptic membrane to release the mediator into the gap; 7 - Ca 2+ is quickly removed from the non-resynaptic ending into the intercellular environment, endoplasmic reticulum and mitochondria

At this moment, voltage-dependent calcium channels open in the membrane and Ca 2+ enters the presynaptic ending, binding to a certain protein on the outer side of the vesicle membrane and starting the process of fusion of the vesicle and the presynaptic membrane. The vesicle can, firstly, integrate into it entirely and “throw out” all its contents into the synaptic cleft (“complete fusion”). Secondly, a short-term contact (“fusion pore”) of special proteins can be formed between the vesicle membrane and the terminal membrane. Through the pore of fusion, some of the mediator molecules manage to enter the synaptic cleft (this method of mediator secretion is called " kiss and run" (translated from English, "kiss and run").

As soon as the mediator is in the gap, it is necessary to quickly remove the calcium that has entered the nerve ending. For this, there are special calcium-binding buffer proteins, as well as calcium pumps that pump calcium into the endoplasmic reticulum, into mitochondria, and into the external environment. At this time, devastated ( kiss and run) or the vesicles re-forming in the nerve ending are again filled with mediator molecules.

Transmitter molecules that have entered the synaptic cleft reach the postsynaptic membrane by diffusion and interact with receptors. Traditionally, the term "receptor" denotes special cells or cellular sensitive formations that respond to stimuli of the external and internal environment: photoreceptors, mechanoreceptors, etc. In modern biology, the term "receptor" is also used in relation to protein molecules embedded in the cell membrane or located in the cytoplasm and capable of responding by changing their shape and state to the effects specific to each type of receptor. Receptors have been found for mediators, hormones, antibodies, and other signaling molecules important for information transmission in living systems.

Transmission of a signal across a membrane involves three steps:

• 1) interaction of the signal molecule with the receptor;
• 2) a change in the shape (conformation) of the receptor molecule, leading to changes in the activity of specialized membrane mediator proteins;
• 3) the formation in the cell of molecules or ions (secondary messengers, or secondary messengers), which activate or, on the contrary, inhibit certain intracellular mechanisms, changing the activity of the entire cell.

Allocate two main types receptors - ionotropic (channel) and metabotropic.

An example channel receptor can serve as a ligand-activated (chemosensitive) receptor for ACh, located on the membrane of skeletal muscle fibers (see Fig. 8.17). Such receptors, in addition to natural ACh, are activated by the tobacco alkaloid nicotine. Therefore, they are called nicotinic or H-cholinergic receptors. In addition to striated muscles, such receptors are also found in the central nervous system. The channel consists of five protein subunits assembled into a kind of tube penetrating the membrane through. The two subunits are the same and are designated a. When two molecules of the mediator ACh are attached to special binding sites on the a-subunits, the channel opens for Na + and Ca 2+ cations (Fig. 9.6).

As a result, an EPSP develops on the postsynaptic membrane, and the cell can become excited. The interaction of the mediator with the receptor lasts 1-2 ms, and then the mediator molecule must be detached, otherwise the receptor will “lose sensitivity” and temporarily cease to react.

gyrate to new portions of the mediator. The channel type of reception is very fast, but it is reduced either to depolarization of the postsynaptic cell by opening cation channels, or to hyperpolarization by opening chloride channels.

Rice. 9.6.

A- building diagram; 6 - cap.;: closed; V- the channel is open; A - angstrom (1SG 10 m)

Metabotropic receptors are protein molecules that are "pulled" through the cell membrane seven times, forming three loops inside the cell and three on the outside of the cell membrane (Fig. 9.7).

Rice. 9.7.

A, p, y - subunits G-white ka

Many similar receptor proteins have now been discovered, with the portion of the protein molecule facing the inside of the cell bound to the corresponding G protein. G proteins are named for their ability to break down GTP (guanosine triphosphate) to GDP (guanosine diphosphate) and a phosphoric acid residue. These proteins consist of three subunits: a, p, y (see Fig. 9.7), and several subtypes of a-subunits are known. One or another subtype of a-subunits that make up the G-protein determines which process in the cell will be affected by this G-protein. For example, Gj.-protein (i.e., including a 5 subunit) stimulates the AC enzyme, G q stimulates phospholipase C, G 0 binds to ion channels, Gj inhibits the activity of blood pressure. Often one type of G-protein affects several processes in the cell. In the absence of a ligand (mediator or hormone) that can bind to the metabotropic receptor, G protein inactive. If the corresponding activating ligand binds to the receptor, the a-subunit is activated (GDP is replaced by GTP), detaches from the Py subunit complex, and interacts with target proteins for a short time, starting or, conversely, inhibiting intracellular processes. The G-protein subunits cannot exist separately for a long time, and after hydrolysis of GTP by the α-subunit, they form a single inactive G-protein. Acting on a number of enzymes and ion channels, activated G-proteins trigger a cascade of intracellular chemical reactions, as a result of which the concentration of a number of regulatory molecules changes - secondary intermediaries(primary mediators - molecules that carry a signal from cell to cell, i.e. mediator, hormone).

The most common second messengers (messengers) include cAMP, which is formed from ATP under the action of the enzyme AC. If, as a result of the action of the ligand on the receptor, the G^-form of the protein is activated, then it activates the enzyme phospholipase C, which in turn stimulates the formation of two mediators from membrane phospholipids: IP 3 (inositol triphosphate) and DAG (diacylglycerol). Both mediators lead to an increase in the concentration of calcium in the cell due to its intake from the outside (through ion channels) or when it is released from intracellular depots. Ca 2+ is the most powerful intracellular stimulator of cell vital processes. In addition, IF-3 and DAG stimulate cell growth, promote gene expression, mediator release, hormone secretion, and so on. However, the second messenger directly or through a number of intermediate stages affects chemosensitive ion channels - it opens or closes them. This contributes to the development of excitation or inhibition of the cell, depending on which channels were affected. The magnitude and duration of the potentials will depend on the type, quantity and time of interaction of the mediator molecules with receptors, and ultimately on which system of secondary messengers is activated under the action of the mediator.

A characteristic feature of metabotropic reception is its cascading, which makes it possible to multiply the effect of the mediator on the cell (Fig. 9.8).

Rice. 9.8.

As already mentioned, the mediator should not interact with the ionotropic or metabotropic receptor for longer than 1–2 ms. In neuromuscular synapses, ACh is rapidly degraded by the enzyme acetylcholinesterase to choline and acetate. The resulting choline is transported to the presynaptic ending and is again used for the synthesis of ACh. Similarly, other mediators (ATP, peptides) are destroyed by the corresponding enzymes in the synaptic cleft.

Another common way to eliminate the neurotransmitter from the synaptic cleft is its reuptake (eng. reuptake) to the presynaptic ending or to glial cells. NA, D and serotonin after being captured by the endings are again “packed” into vesicles or can be destroyed by intracellular enzymes. GABA and glutamate are transported from the synaptic cleft to glial cells and, having undergone a series of biochemical transformations, again enter the nerve endings.

In the process of evolution, nature has created many physiologically active substances that act on the metabolism of mediators. Many of these substances are produced by plants for defense purposes. At the same time, poisons that affect the life cycle of neurotransmitters and synaptic transmission are produced by some animals: to attack the prey or to defend against predators.

A huge number of chemical compounds that affect the operation of mediator systems are artificially created by man in search of new drugs that affect the functioning of the NS.

• See paragraph 10.3.

7.4. MEDIATORS AND RECEPTORS OF THE CNS

CNS mediators are many structurally heterogeneous chemical substances (about 30 biologically active substances have been found in the brain to date). The substance from which the neurotransmitter (precursor of the mediator) is synthesized enters the neuron or its ending from the blood or cerebrospinal fluid, as a result of biochemical reactions under the action of enzymes it turns into the corresponding mediator, then is transported to synaptic vesicles. According to their chemical structure, they can be divided into several groups, the main of which are amines, amino acids, polypeptides. Sufficiently wide

The most common mediator is acetylcholine.

A. Acetylcholine found in the cerebral cortex, in the trunk, in the spinal cord, known mainly as an excitatory mediator; in particular, it is a mediator of a-mo-toneurons of the spinal cord that innervates skeletal muscles. With the help of acetylcholine, a-motoneurons through the collaterals of their axons transmit an excitatory effect on Renshaw's inhibitory cells. In the reticular formation of the brain stem, in the hypothalamus, M- and H-cholinergic receptors were found. The CNS has 7 types of H-cholinergic receptors. In the central nervous system, the main M-cholinergic receptors are M g and M 2 receptors. M,-ho-linoreceptors localized on the neurons of the hippocampus, striatum, cerebral cortex. M 2 -cholinergic receptors localized on the cells of the cerebellum, brain stem. N-cholinergic receptors quite densely located in the hypothalamus and tires. These receptors have been studied quite well; they have been isolated using α-bungarotoxin (the main component of the venom of the banded krait) and α-neurotoxin contained in the venom of the cobra. When acetylcholine interacts with the H-cholinergic receptor protein, the latter changes its conformation, as a result of which the ion channel opens. When acetylcholine interacts with the M-cholinergic receptor, the activation of ion channels (K +, Ca 2+) is carried out with the help of second intracellular mediators (cAMP - cyclic adenosine monophosphate for the M 2 receptor and IP3 / DAG - inositol-3-phosphate (diacylglycerol for the M receptor). Acetylcholine activates both excitatory and inhibitory neurons, which determines its effect. The inhibitory effect of acetylcholine ilcholine exerts with the help of M-cholinergic receptors in the deep layers of the cerebral cortex, in the brain stem, caudate nucleus.

B. Amines (dopamine, norepinephrine, serotonin, histamine). Most of them are found in significant quantities in the neurons of the brain stem, and in smaller quantities are detected in other parts of the CNS.

Amines provide the occurrence of processes of excitation and inhibition, for example, in the diencephalon, in the substantia nigra, in the limbic system, in the striatum. Noradrenergic neurons are concentrated mainly in the locus coeruleus (midbrain), where there are only a few hundred of them. But branches of their axons are found throughout the CNS.

Norepinephrine is an inhibitory mediator of Purkinje cells of the cerebellum and peripheral ganglia; excitatory - in the hypothalamus, in the nuclei of the epithalamus. α- and β-adrenergic receptors were found in the reticular formation of the brain stem and hypothalamus.

Dopamine receptors subdivided into D g and D 2 subtypes. D, receptors are localized on the cells of the striatum, act through dopamine-sensitive adenylate cyclase, like D 2 receptors. D2 receptors are found in the pituitary gland. Under the action of dopamine on them, the synthesis and secretion of prolactin, oxytocin, melanocyte-stimulating hormone, and endorphin are inhibited. D2 receptors have been found on striatal neurons, where their function has not yet been determined.

Serotonin. With its help, excitatory and inhibitory influences are transmitted in the neurons of the brain stem, and inhibitory influences are transmitted in the cerebral cortex. There are several types of serotoninoreceptors. Serotonin realizes its influence with the help of ionotropic and metabotropic receptors (cAMP and IFz/DAG). Serotonin is found mainly in structures related to the regulation of autonomic functions. Especially a lot of it in the limbic system, the raphe nuclei. Enzymes involved in the synthesis of serotonin were found in the neurons of these structures. The axons of these neurons pass in the bulbospinal tracts and terminate on neurons of various segments of the spinal cord. Here they contact with cells of preganglionic sympathetic neurons and with intercalary neurons of the gelatinous substance. It is believed that some of these so-called sympathetic neurons (and perhaps all) are serotonergic neurons of the autonomic nervous system. Their axons, according to the latest data, go to the organs of the gastrointestinal tract and stimulate their contractions.

Gnetami n. Its rather high concentration was found in the pituitary gland and the median eminence of the hypothalamus - it is here that the main number of histaminergic neurons is concentrated. In other parts of the central nervous system, the level of histamine is very low. Its mediator role has been little studied. Allocate H, -, H 2 - and H 3 -histamine receptors. H-receptors are present in the hypothalamus and are involved in the regulation of food intake, thermoregulation, secretion of prolactin and antidiuretic hormone. H 2 receptors are found on glial cells. Histamine implements its influence with the help of second intermediaries (cAMP and IF 3 / DAG).

B. Amino acids. Acidic amino acids (glycine, gamma-aminobutyric acid) are inhibitory mediators in the CNS synapses and act on the corresponding receptors (see section 7.8), glycine - in the spinal cord, in the brain stem, GABA - in the cerebral cortex, cerebellum, brain stem, spinal cord. Neutral amino acids (alpha-glutamate, alpha-aspartate) transmit excitatory influences and act on the corresponding excitatory receptors. It is assumed that glutamate can be a mediator of afferents in the spinal cord. Receptors for glutamine and aspartic amino acids are found on the cells of the spinal cord, cerebellum, thalamus, hippocampus, and cerebral cortex. Glutamate is the main excitatory mediator of the CNS (75% of excitatory brain synapses). Glutamate receptors are ionotropic (K + , Ca 2+ , Na +) and metabotropic (cAMP and IPs/DAG).

D. Polypeptides also perform a mediator function in the CNS synapses. In particular, substance P is a mediator of neurons that transmit pain signals. Especially a lot of this polypeptide is found in the dorsal roots of the spinal cord. This served as the basis for the assumption that substance P can be a mediator of sensitive nerve cells in the area of ​​their switching to intercalary neurons. Substance P is found in large quantities in the hypothalamic region. There are two types of substance II receptors: SP-P type receptors located on the neurons of the cerebral septum, and SP-E type receptors located on the neurons of the cerebral cortex.

Enkephalins and endorphins are mediators of neurons that block pain impulses. They exercise their influence through appropriate opiate receptors, which are especially densely located on the cells of the limbic system, there are also many of them on the cells of the substantia nigra, the nuclei of the diencephalon and solitary tract, they are present on the cells of the blue spot, spinal cord. Their ligands are p-endorphin, dynorphin, leu- and me-tenkephalins. Various opiate receptors are designated by the letters of the Greek alphabet: c, k, su, 1, e. K-receptors interact with dynorphin and leu-enkephalin; the selectivity of the action of other ligands on opiate receptors has not been proven.

Angiotensin is involved in the transfer of information about the body's need for water, luliberin - in sexual activity.

ness. Binding of angiotensin to receptors causes an increase in the permeability of cell membranes for Ca 2+ . This reaction is caused not by conformational changes in the receptor protein, but by the processes of phosphorylation of membrane proteins due to the activation of the adenylate cyclase system and changes in the synthesis of prostaglandins. Angiotensin receptors have been found on brain neurons, on cells of the midbrain, diencephalon, and cerebral cortex.

found on brain neurons VIP receptors and receptors for somatostatin. Receptors for cholecystokinin found on the cells of the cerebral cortex, caudate nucleus, olfactory bulbs. The action of cholecystokinin on receptors increases membrane permeability for Ca 2+ by activating the adenylate cyclase system.

D. ATP can also play the role of a classical mediator, in particular in the frenulum neurons (excitatory effect). In the spinal cord, it is secreted along with GABA K, but performs an excitatory function. ATP receptors are very diverse, some of them are ionotropic, others are metabotropic. ATP and adenosine are involved in the formation of pain, limit the overexcitation of the central nervous system.

E. Chemicals circulating in the blood(some hormones, prostaglandins), which have a modulating effect on the activity of synapses. Prostaglandins - unsaturated hydroxycarboxylic acids released from cells affect many parts of the synaptic process, for example, the secretion of a mediator, the work of adenylate cyclases. They have a high physiological activity, but are quickly inactivated and therefore act locally.

G. Hypothalamic neurohormones. regulating the function of the pituitary gland, also perform mediator role.

Physiological effects of the action of some mediators of the brain. H about r-adrenaline regulates mood, emotional reactions, ensures the maintenance of wakefulness, participates in the mechanisms of formation of some phases of sleep, dreams; dopamine - in the formation of a sense of pleasure, the regulation of emotional reactions, maintaining wakefulness. Striatal dopamine regulates complex muscle movements. Seroton accelerates the learning process, the formation of pain, sensory perception, falling asleep; angiotensin -

increase in blood pressure, inhibition of the synthesis of catechol-amines, stimulates the secretion of hormones, informs the central nervous system about the osmotic pressure of the blood. Oligopeptides - mediators of mood, sexual behavior; transmission of nociceptive excitation from the periphery to the central nervous system, the formation of pain sensations. Endorphins, enkephalins, a peptide that causes delta a-c on n, give anti-pain reactions, increase resistance to stress, sleep. Prostaglandins cause an increase in blood clotting; a change in the tone of smooth muscles, an increase in the physiological effect of mediators and hormones. Brain-specific proteins in different parts of the brain influence learning processes.

According to the Dale principle, one neuron synthesizes and uses the same neurotransmitter in all branches of its axon ("one neuron - one neurotransmitter"). In addition to the main mediator, as it turned out, others can be released in the endings of the axon - accompanying mediators (mediators) that play a modulating role or act more slowly. However, in the spinal cord, two fast-acting typical mediators are installed in one inhibitory neuron - GAM K and glycine, and even one inhibitory (GABA.) And one excitatory (ATP). Therefore, the Dale principle in the new edition first sounded like this: "One neuron - one fast neurotransmitter", and then: "One neuron - one fast synaptic effect."

The effect of the action of the mediator depends mainly on the properties of the ion channels of the postsynaptic membrane. This phenomenon is especially clearly demonstrated when comparing the effects of individual mediators in the central nervous system and in the peripheral synapses of the body. Acetylcholine, for example, in the cerebral cortex with microapplications to different neurons can cause excitation and inhibition, in the synapses of the heart - inhibition, in the synapses of the smooth muscles of the gastrointestinal tract - excitation. Catecholamines stimulate cardiac activity, but inhibit contractions of the stomach and intestines.

Intercellular interaction is realized not only with the help of well-studied mediators, but also with the help of numerous substances that, at low concentrations, change intracellular biochemical processes in neurons, activate glial cells, and change the response of a neuron to a mediator. All these substances are called "information substances". Chemical transmission of signals in the nervous system can occur both at the “anatomical address” (implemented in synapses with the help of classical mediators) and at the “chemical address”. In the latter case, the cells synthesize and secrete various informational substances into the intercellular fluid or blood, which are directed by slow diffuse movement to target cells, which can be located at a considerable distance from the place of substance synthesis.

The study of mediator processes is one of the tasks of neurochemistry, which in recent decades has made significant progress in understanding the underlying mechanisms of the nervous system in normal and pathological conditions. Achievements in neurochemistry formed the basis for the development of neuro- and psychopharmacology, neuro- and psychoendocrinology.

Information substances of the nervous system can be classified according to different criteria. We restrict ourselves to dividing them into two groups: 1) classical mediators, released in the presynaptic ending and directly transmitting excitation in the synapse and 2) modulators , or regulatory peptides that change the cell's response to classical mediators or other forms of nerve cell activity (although some of them may also perform a transfer function).

Classic Picks

Acetylcholine (AH) - one of the first studied mediators. Its molecule consists of the nitrogen-containing substance choline and the remainder of acetic acid. ACh works as a mediator in three functional blocks of the nervous system: 1) in neuromuscular synapses of skeletal muscles (synthesized in motor neurons); 2) in the peripheral part of the ANS (synthesized in preganglionic sympathetic and parasympathetic neurons, postganglionic parasympathetic neurons); 3) in the cerebral hemispheres, where the cholinergic systems are represented by neurons of some reticular nuclei of the bridge, interneurons of the striatum, neurons of the nuclei of the transparent septum. The axons of these neurons travel to various structures in the forebrain, primarily to the neocortex and hippocampus. Recent research results show that the cholinergic system plays an important role in learning and memory. Thus, in the brains of deceased people suffering from Alzheimer's disease, there is a sharp decrease in the number of cholinergic neurons in the cerebral hemispheres.

Synaptic receptors for ACh are divided into nicotine(excited by ACh and nicotine) and muscarinic(excited by ACh and fly agaric toxin muscarine). Nicotinic receptors open sodium channels and lead to the formation of EPSPs. They are located in the neuromuscular synapses of the skeletal muscles, in the autonomic ganglia, and a little in the central nervous system. The autonomic ganglia are most sensitive to nicotine, so the first attempts at smoking lead to pronounced autonomic manifestations - blood pressure drops, nausea, dizziness. In process of accustoming remain basically sympathetic action. Nicotinic receptors are also present in the central nervous system, due to which nicotine, being a psychoactive substance, has a central stimulating effect. Antagonists of nicotinic receptors - compounds similar to the poison curare - act mainly on neuromuscular synapses, causing paralysis of the skeletal muscles. Muscarinic receptors are located in the synapses of autonomic postganglionic (mainly parasympathetic) neurons, in the CNS. Their excitation can open both potassium and sodium channels. A classic muscarinic receptor antagonist is atropine, which causes sympathetic effects, motor and speech excitation, and hallucinations. ACh is inactivated by the enzyme acetylcholinesterase. Reversible blockers of this enzyme improve neuromuscular transmission and are used in neurological practice, irreversible blockers cause dangerous poisoning (chlorophos, nerve gases).

Biogenic amines (BA) - a group of mediators containing an amino group. They are divided into catecholamines (norepinephrine, dopamine) and serotonin.

Norepinephrine (NA) in the peripheral NS it is synthesized in the neurons of the sympathetic ganglia, in the CNS - in the blue spot and the interpeduncular nucleus of the midbrain. The axons of the cells of these nuclei are widely distributed in various structures of the brain and spinal cord. Excitation of adrenergic receptors can increase both sodium (EPSP) and potassium (TPSP) conduction. Agonists of NA-ergic synapses are ephedrine and other drugs for bronchial asthma, vasoconstrictor drugs - naphthyzine, galazolin. Antagonists are drugs used to lower blood pressure (blockers).

In the CNS, the effects of NA are:

Increasing the level of wakefulness;

Inhibitory regulation of sensory flows, anesthesia;

Increasing the level of physical activity;

Increased aggressiveness, sthenic emotions during stress reactions (excitement, pleasure from risk, overcoming fatigue). In some forms of depression, there is a decrease in the level of NA, and many antidepressants stimulate its formation.

Dopamine (YES) – immediate predecessor of HA. It functions in the central nervous system, where three main DA-ergic systems are distinguished:

1) black substance - striatum. The main function of this system is to maintain the general level of motor activity, ensure the accuracy of the execution of motor programs, and eliminate unnecessary movements. Lack of dopamine in this system leads to the development of parkinsonism;

2) reticular nuclei of the midbrain tegmentum - KBP (new, old, ancient). Regulates emotional and thought processes, "responsible" for positive emotions, which are most often associated with the pleasure of movement, provides orderliness and consistency of thought processes. Deficiency in this system can lead to the development of depression; excessive activity (in particular, a large number of DA receptors) is observed in some forms of schizophrenia;

3) hypothalamus - pituitary gland. Participates in the regulation of the hypothalamic-pituitary system (in particular, DA inhibits the secretion of prolactin), causes inhibition of the centers of hunger, aggressiveness, sexual behavior, excitation of the pleasure center.

Drugs that block dopamine receptors are used in medicine as antipsychotics. Hazardous psychoactive substances such as psychostimulants and cocaine enhance the effect of DA (increase release or block neurotransmitter reuptake).

Serotonin belongs to the same chemical group as the catecholamines. Serotonin is not only a mediator, but also a tissue hormone with numerous functions: it causes a change in the lumen of blood vessels, enhances gastrointestinal motility, tone of the uterus, bronchial muscles, is released from platelets when blood vessels are injured and helps stop bleeding, is one of the inflammation factors. In the CNS, it is synthesized in the raphe nuclei. Axons of serotonergic neurons terminate in the striatum, neocortex, structures of the limbic system, midbrain nuclei, and spinal cord. From this it follows that serotonin affects almost all brain functions. Indeed, the participation of serotonin in the regulation of the level of wakefulness, the work of sensory systems, learning, emotional and motivational processes has been established. In the sleep-wake system, serotonin competes with catecholamines, causing a decrease in the level of wakefulness (the raphe nucleus is one of the centers of sleep). In sensory systems, serotonin has an inhibitory effect, which explains its analgesic effect (in the posterior horns of the spinal cord, it activates inhibitory neurons). In the cortical zones of sensory systems, it limits the excessive spread of sensory signals, providing "focusing" of the signal. The blockade of this mechanism can greatly distort the processes of perception, up to the appearance of illusions and hallucinations. Serotonin has a similar effect in the associative zones of the cortex, "organizing" integrative processes, in particular, thinking. Participates in learning processes, and to a greater extent, if the development of reflexes is associated with positive reinforcement (reward), while norepinephrine helps to consolidate those forms of behavior that are aimed at avoiding punishment. In the emotional and motivational sphere, serotonin has a calming effect (reducing anxiety, appetite). Of interest is one of the groups of substances that block serotonin receptors - lysergic acid derivatives (ergot alkaloids). They are used in medicine (stimulation of the uterus, with migraine) and are the active principle of hallucinogens (LSD is a synthetic hallucinogen).

Inactivation of serotonin, like other biogenic amines, occurs under the action of the enzyme monoamine oxidase (MAO). Interestingly, such a psychological feature of people as the desire to search for new strong sensations may be associated with a small amount of this enzyme in the central nervous system. MAO inhibitors or serotonin reuptake inhibitors are used in medicine as antidepressants.

Amino acid mediators (AA). More than 80% of CNS neurons use amino acid mediators. AAs are quite simple in their composition, characterized by a greater specificity of synaptic effects (they have either excitatory properties - glutamic and aspartic acids, or inhibitory properties - glycine and GABA).

Glutamic acid (HA) – the main excitatory neurotransmitter of the CNS. It is present in any protein food, but food HA normally penetrates very poorly through the blood-brain barrier, which protects the brain from failures in its activity. Almost all of the HA required by the brain is synthesized in the nervous tissue. However, when eating a large amount of HA salts, its neurotropic effect can be observed: the central nervous system is activated, and this is used in the clinic, prescribing glutamate tablets (2-3g) for mental retardation or exhaustion of the nervous system. Glutamate is widely used in the food industry as a flavoring agent, and is included in food concentrates, sausages, etc. (has a meaty taste). With the simultaneous use of 10-30 g of glutamate with food, excessive excitation of the vasomotor center may occur, blood pressure rises, and the pulse quickens. This is dangerous for health, especially for children and people suffering from cardiovascular diseases. GC antagonists, such as calypsol (ketamine), are used clinically as powerful analgesics and rapid anesthesia agents. A side effect is the appearance of hallucinations. Some substances in this group are strong hallucinogenic drugs.

Inactivation of HA occurs by uptake by astrocytes, where it is converted into aspartic acid and GABA.

Gamma-aminobutyric (GABA) – non-food AA (completely synthesized in the body). Plays an important role in intracellular metabolism; only a small part of GABA performs mediator functions. It is a mediator of small inhibitory neurons widely distributed in the central nervous system. This mediator is also used by Purkinje cells, globus pallidus neurons. Opens Ka + and Cl - channels on the postsynaptic membrane. GABA receptors have a complex structure, they have centers that bind to other substances, which leads to a change in the effects of the mediator. Such substances are used as sedatives and tranquilizers, hypnotics, antiepileptics, and anesthetics. Sometimes the same substance can cause all these effects depending on the dose. For example, barbiturates, which are used for anesthesia (hexenal), in severe forms of epilepsy (benzonal, phenobarbital). In smaller doses, they act as hypnotics, but are used to a limited extent, since they disrupt the normal structure of sleep (shorten the paradoxical phase), after such sleep, lethargy and impaired coordination of movements persist for a long time. Prolonged use of barbiturates causes drug dependence. Alcohol enhances the effect of barbiturates, overdose easily occurs, leading to respiratory arrest. Another group of GABA agonists are the benzodiazepines. They act more selectively and gently, as sleeping pills increase the depth and duration of sleep (Relanium, Phenazepam). Large amounts also cause lethargy after sleep. GABA agonists are used as tranquilizers (calming) or anxiolytics (reducing anxiety). Dependence formation is possible. GABA-based drugs are used as mild psychostimulants for age-related changes, vascular diseases, mental retardation, after strokes and injuries. They act by improving the work of interneurons and belong to the group of nootropics that improve learning and memory, increase the resistance of the central nervous system to adverse effects, and restore impaired brain functions (aminalon, pantogam, nootropil). As with all neurotropic drugs, they should only be used for strict medical reasons.

Glycine – an inhibitory neurotransmitter, but less common than GABA. Glycinergic neurons mainly inhibit motor neurons and protect them from overexcitation. The antagonist of glycine is strychnine (a poison that causes convulsions and suffocation). Glycine is used as a calming agent and improves brain metabolism.

Modulating mediators

Purines - substances containing adenosine. They affect the presynaptic membrane, reducing the release of the neurotransmitter. ATP, ADP, AMP have the same effect. The physiological role is to protect the nervous system from exhaustion. If these receptors are blocked, many mediator systems are activated, the nervous system will work "to the stop". Caffeine, theobromine, theophylline (coffee, tea, cocoa, cola nuts) have this effect. With a large dose of caffeine, the reserves of mediators are quickly depleted, and “outrageous inhibition” sets in. With the constant introduction of caffeine, the number of purine receptors increases, so the refusal of coffee causes depression and drowsiness.

Peptide mediators- substances consisting of short amino acid chains.

Substance P (from the English powder - powder: it was isolated from the dry powder of the spinal cord of cows). It is produced in the neurons of the spinal ganglia involved in the conduction of pain impulses. In the neurons of the posterior horns of the spinal cord, substance P works together with glutamic acid as a classical neurotransmitter, transmitting pain signals. It is found in the sensitive endings of the skin, from where it is released when damaged, causing an inflammatory process. It is also produced by some interneurons of the CNS, acting as a modulating mediator.

Opioid peptides – substances like opium. Opium is an alkaloid of the soporific poppy. The active substance is morphine, which causes pain relief (through the posterior horns of the spinal cord), euphoria (stimulation of the pleasure center of the hypothalamus), falling asleep (inhibition of stem structures). Overdose leads to inhibition of the respiratory center. Such a fast and strong effect of morphine is due to the fact that there are opiate receptors in the central nervous system, which were discovered in the 70s of the 20th century. Later, several varieties of opioid peptides were discovered. Their main mechanism of action is presynaptic inhibition of mediator release. The biochemical processes in the cell very quickly adapt to the action of opiates, and an increasing dose is needed to achieve the effect. With the refusal of morphine, neurons have a "reserve" of substances that facilitate the transmission of signals, so pain and other impulses are carried out very intensively, which causes the onset of "withdrawal" in the withdrawal syndrome. Morphine has been widely used for pain relief since the 19th century, especially during wars in hospitals. A side effect was the formation of addiction. The synthesis of heroin was the result of attempts to create a less dangerous painkiller. It was 10 times more active than morphine, but it soon turned out that the rate of addiction to heroin was even higher than to morphine, and in the 1920s heroin was banned for use, passing into the category of drugs. Morphine-like drugs are used for pain relief in the most severe cases (narcotic analgesics). In addition to morphine, codeine (also a poppy alkaloid) is used, which has an antitussive effect.

In addition to these, the functions of modulating mediators are performed by some hypothalamic, pituitary and tissue hormones. For example, thyroliberin causes emotional activation, an increase in the level of wakefulness, and stimulates the respiratory center. Cholecystokinin - causes anxiety and fear. Vasopressin - activates memory. ACTH - stimulates attention and improves metabolic processes in nerve cells. There are neuropeptides that selectively control sexual behavior, food motivation, and thermoregulation. All of them form a complex hierarchical system of interactions that finely regulates the work of the central nervous system.

Lecture 5. FEATURES OF BRAIN CIRCULATION. CSF AND HEMATOENCEPHALIC BARRIER

Blood supply to the brain and spinal cord

The work of the brain is associated with high energy costs. The brain makes up about 2% of body weight, but 15% of the blood ejected by the heart into the aorta in one contraction enters the vessels of the brain. Violation of cerebral circulation inevitably affects the functioning of the nervous system.

The brain is supplied with arterial blood from two main sources - the internal carotid arteries, branching from the common carotid arteries, originating from the aortic arch, and from the vertebral arteries, branching from the subclavian arteries. The common carotid and subclavian arteries originate from the aortic arch.

Internal carotid arteries- large vessels, their diameter is about 1 cm. They enter the cranial cavity through the jugular foramina in the temporal bones, pass through the dura mater, branch out and supply blood to the eyeballs, visual tracts, diencephalon, basal nuclei, frontal parietal, temporal, insular lobes of the cerebral hemispheres. The largest branches anterior and middle cerebral arteries.

Vertebral arteries start from the subclavian arteries at the level of the 7th cervical vertebra, go up through the transverse foramina of the cervical vertebrae and penetrate into the cranial cavity through the foramen magnum. The branches of these arteries supply the spinal cord, medulla oblongata and cerebellum, as well as the meninges. At the posterior edge of the pons, the right and left vertebral arteries join to form the basilar artery, which runs in the sulcus of the same name on the ventral surface of the pons. At the anterior margin of the pons, the basilar artery divides into two posterior cerebral arteries. Its branches supply blood to the pons, cerebellum, medulla oblongata, midbrain, partially diencephalon, and occipital lobes of the cerebral hemispheres.

On the basis of the brain, the branches of the internal carotid artery and the basilar artery are interconnected, forming arterial (willisian) circle of the brain. This circle is located in the subarachnoid space and covers the optic chiasm and hypothalamus. Thanks to this circle, blood flows to different parts of the brain are equalized, even if one of the vessels (carotid or vertebral artery) is pinched or underdeveloped.

The spinal cord is supplied with blood by branches of the vertebral arteries (cervical segments), as well as by branches of the thoracic and abdominal aorta.

The branches of the cerebral arteries are located in the pia mater, which is also called the vascular, and together with its fibers penetrate into the brain tissue, where they branch into small arterioles and capillaries.

Capillaries are the smallest vessels, the wall of which consists of a single layer of cells. Through this wall, substances dissolved in the blood penetrate into the brain tissue, and the products of brain metabolism pass into the blood. Capillaries are collected in venules, then in the veins lying in the choroid of the brain. Thin blood vessels of the pia mater penetrate into the ventricles of the brain, where they form the choroid plexuses. Ultimately, venous blood flows into the sinuses of the dura mater, from where it enters the large veins of the systemic circulation.

GABA - gamma-aminobutyric acid - is the main inhibitory neurotransmitter in the brain, it is involved in both postsynaptic and presynaptic inhibition. GABA is formed from glutamate under the influence of glutamate decarboxylase and interacts with two types of GABA receptors on postsynaptic synaptic membranes: a) when interacting with GABA receptors, the permeability of membrane ion channels for SG ions increases, which occurs in clinical practice with the use of barbiturates; b) when interacting with GABAB receptors, the permeability of ion channels for K + ions increases. Glycine - an inhibitory neurotransmitter secreted primarily by neurons in the spinal cord and brainstem. It increases the conductivity of the ion channels of the postsynaptic membrane for SG ions, which leads to the development of hyperpolarization - HPSP. Glycine antagonist is strychnine, the introduction of which leads to muscle hyperactivity and judgment, which confirms the important role of postsynaptic inhibition in the normal function of the central nervous system. Tetanus toxin also causes seizures. acting on protein synaptobrevin membranes of vesicles, it blocks the exocytosis of the presynaptic inhibitory neurotransmitter, resulting in a sharp excitation of the central nervous system.

electrical synapses

Interneuronal transmission of excitation can also occur electrically, that is, without the participation of mediators. The condition for this is a tight contact between two cells up to 9 nm wide. So, the sodium current from one of them can pass through the open channels of the other membrane. That is, the source of the postsynaptic current of the second neuron is the presynaptic membrane of the first. The process is mediator-free; provided exclusively by channel proteins (lipid membranes are impermeable to ions). It is these intercellular connections that are called Nexus (gap junctions). They are located strictly opposite each other in the membranes of two neurons - that is, on the same line; large in diameter (up to 1.5 nm in diameter), transmissive even for macromolecules weighing up to 1000 Consist of subunits weighing up to 25000, their presence is common for the CNS of both vertebrates and invertebrates; inherent in groups of synchronously functioning cells (in particular, found in the cerebellum between granule cells).

Most electrical synapses are excitatory. But with certain morphological characteristics, they can be inhibitory. With bilateral conduction, some of them have a rectifying effect, that is, they conduct electric current much better than presynaptic structures to postsynaptic ones than in the opposite direction.

Conducting impulses across synapses

Each nerve center has its own morphological and functional specifics. But the neurodynamics of any of them is based on a number of common features. They are associated with the mechanisms of transmission of excitation in synapses; with the interaction between the neurons that make up this center; with genetically programmed functional features of neurons and connections between them.

Features of the conduction of excitation through synapses are as follows.

1 One-sidedness of excitation. In the axon, excitation passes in both directions from the place of its origin, in the nerve center - only in one direction: from the receptor to the effector (i.e., at the level of the synapse from the presynaptic membrane to the postsynaptic), which is explained by the structural and functional organization of the synapse, namely, the absence of synaptic vesicles with a mediator in postsynaptic neurons, 2 Snap delay in excitation. excitation in the nerve center is carried out at a lower speed than in other parts of the reflex arc. This is due to the fact that it is spent on the processes of mediator release, with the physicochemical processes that occur in the synapse, with the occurrence of EPSPs and the generation of AP. All this in one synapse takes 0.5-1 ms. This phenomenon is called synaptic delay in the conduction of excitation. The more complex the reflex arc, the more synapses and, accordingly, the greater the synaptic delay.

The sum of synaptic delays in the reflex arc is called the present tense of the reflex. The time from the beginning of the action of the stimulus to the appearance of a reflex response is called the latent, or latent period (LP) of the reflex. The duration of this period depends on the number of neurons, and hence the synapses involved in the reflex. For example, a tendon knee jerk, the reflex arc of which is monosynaptic, has a latency of 24 ms, a visual or auditory reaction is 200 ms.

Depending on whether excitatory or inhibitory neurons make synaptic contacts, the signal can be amplified or suppressed. The mechanisms of interaction between excitatory and inhibitory influences on a neuron underlie their integrative function.

Such a mechanism of interaction is the summation of excitatory influences on the neuron - excitatory postsynaptic potential (EPSP), or inhibitory influences - inhibitory postsynaptic potential (IPSP), or both excitatory (EPSP) and inhibitory (GPSP).

3 Summation of nervous processes - the phenomenon of the occurrence of excitation under certain conditions of application of subthreshold irritations. Summation is described by I. M. Sechenov. There are two types of summation: temporal summation and spatial summation (Fig. 3.15).

Time summation - the occurrence of excitation on a number of subthreshold stimuli that sequentially enter the cell or center from one receptor field (Fig. 3.16). The stimulus frequency should be

RICE. 3.15. summation of excitation. A - time summation. B - spatial summation

RICE. 3.16.

so that the interval between them is no more than 15 ms, that is, the duration of the EPSP is shorter. Under such conditions, the EPSP for the next stimulus develops before the EPSP for the previous stimulus ends. EPSPs are summed up, their amplitude grows and, finally, when a critical level of depolarization is reached, AP occurs.

Spatial summation - the emergence of excitation (EPSP) with the simultaneous application of several pre-threshold stimuli to different parts of the receptor FIELD (Fig. 3.17).

If EPSPs occur simultaneously in several neuron synapses (at least 50), the neuron membrane depolarizes to critical values ​​and, as a result, AP occurs. Spatial summation of excitation (EPSP) and inhibition (GPSP) processes ensures the integrative function of neurons. If inhibition predominates, information is not transmitted to the next neuron; if excitation prevails, information is transmitted further to the next neuron due to the generation of AP on the axon membrane (Fig. 3.18).

4 Transformation of the rhythm of excitation - this is a discrepancy between the frequency of AP in the afferent and efferent links of the reflex arc. For example, in response to a single stimulus applied

RICE. 3.17.

RICE. 3.18.

to the afferent nerve, the centers along the efferent fibers send a whole series of impulses to the working organ one after another. In another situation, at a high stimulation frequency, a much lower frequency arrives at the effector.

5 Aftereffect of excitation - the phenomenon of continuation of excitation in the central nervous system after the cessation of irritation. The short-term aftereffect is associated with a long duration of the critical level EPSP. The long aftereffect is due to the circulation of excitation by closed nerve circuits. Such a phenomenon is called reverb. Due to the reverberation of excitations (PD), the nerve centers are constantly in a state of tone. The development of reverberation at the level of the whole organism is important in the organization of memory.

6 Posthetanic potentiation - the phenomenon of the appearance or strengthening of the response to individual testing sensory stimuli for some time after the previous weak frequent (100-200 NML / s) rhythmic stimulation. Potentiation is due to processes at the level of the presynaptic membrane and is expressed by an increase in the release of the mediator. This phenomenon has a homosynaptic nature, that is, it occurs when rhythmic stimulation and a testing impulse arrive at the neuron along the same afferent fibers. The potentiation is based, first of all, on the increase in the entry of Ca2f through the presynaptic membrane. This phenomenon is progressively increasing with every impulse. And when the amount of Ca 2+ becomes greater than the ability of mitochondria and the endoplasmic reticulum to absorb them, a prolonged release of the mediator into the synapse occurs. Consequently, there is a mobilization of readiness for the release of the mediator by a large number of vesicles and, as a result, an increase in the number of mediator quanta on the postsynaptic membrane. According to modern data, the secretion of endogenous neuropeptides plays an important role in the genesis of post-tetanic potentiation, especially during the transition of short-term potentiation to long-term one. Among them are neuromodulators that act on both the presynaptic and postsynaptic membranes. Stimulants are somatostatin, growth factor, and inhibitors are interleukin, thyroliberin, melatonin. Also significant are arachidonic acid, NO. Potentiation matters in the organization of memory. Thanks to reinforcing circuits, learning is organized.

7 Fatigue nerve centers. With prolonged repeated performance of the same reflex, after a while, a state of decrease in the strength of the reflex reaction occurs and even its complete suppression, that is, fatigue sets in. Fatigue primarily develops in the nerve center. It is associated with impaired transmission in synapses, depletion of mediator resources in presynaptic vesicles, a decrease in the sensitivity of subsynaptic membrane receptors to mediators, and a weakening of the action of enzyme systems. One of the reasons is the "addiction" of the postsynaptic membrane to the action of the mediator - habituation.

Some chemicals have a specific effect on the corresponding nerve centers, which is associated with the structures of these chemicals, which may be related to the corresponding neurotransmitters of the nerve centers.

Among them:

1 narcotics - those used in surgical practice for anesthesia (chloroethyl, ketamine, barbiturates, etc.);

2 tranquilizers - sedatives (relanium, chlorpromazine, trioxazine, amizil, oxylidine, among herbal preparations - infusion of motherwort, peony, etc.);

3 neurotropic substances of selective action (lobelin, cytiton - causative agents of the respiratory center; apomorphine - the causative agent of the center of vomiting; mescaline - visual hallucinogen, etc.).