The occurrence of AP as a result of the artificial depolarizing effect of electric current was discussed above. Naturally, in real conditions, PD is generated as a result of certain physiological processes. These processes take place in synapses. When the AP, spreading across the membrane, reaches the presynaptic terminal, this leads to the release of the transmitter into the synaptic cleft.

On the postsynaptic membrane are receptors- complex protein molecules with which the mediator is able to connect. The resulting complex is the “triggering link” in the chain of biochemical reactions leading to the opening chemosensitive ion channels. Thanks to such channels - sodium, potassium, chloride, calcium - postsynaptic potentials (PSPs), both excitatory and inhibitory, are generated. Chemosensitive ion channels typically open for 3–5 ms.

Different mediators cause the opening of different channels. The opening of sodium or calcium channels on the postsynaptic membrane causes the entry of Na + ions (Ca 2+) into the cell and a slight depolarization of the neuron. During this depolarization, the potential difference across the membrane is closer to the AP triggering threshold. Therefore, a smaller-than-usual stimulus can cause the neuron to respond—that is, the nerve cell is in a relatively excited state. In this regard, local depolarization of the membrane under the influence of a mediator was called excitatory postsynaptic potential(EPSP).

The opening of chemosensitive Cl - channels leads to the entry of chlorine ions into the cell; opening of K + channels – to the exit of potassium ions. In both cases, a slight hyperpolarization occurs, and the potential difference across the neuron membrane increases in absolute value. Against this background, a greater than usual stimulus is required to trigger PD. Consequently, the nerve cell is in a relatively inhibited state. In this regard, local hyperpolarization of the membrane under the influence of a mediator was called inhibitory postsynaptic potential(TPSP).

In contrast to the action potential, postsynaptic potentials (PSPs) do not develop according to the “all or nothing” law, but gradually, i.e. may be more or less. The magnitude of the PSP is proportional to the amount of transmitter released into the synaptic cleft. The mediator is released from the presynapse in small portions - quanta, corresponding to the volume of the vesicle. Each vesicle contains several thousand mediator molecules. Accordingly, one quantum of the mediator causes a small PSP (miniature PSP), with a value of 0.1-0.6 mV. Another difference between PSP and AP is that PSP do not spread across the neuron membrane.

The averaged parameters of EPSP and IPSP are close. Their duration is usually about 10 ms (sometimes 50-100 ms), which is significantly longer than in the case of PD. The amplitude of EPSPs and IPSPs is determined by the duration and slope of their first phase. It, in turn, depends on the amount and duration of presence of the transmitter in the synaptic cleft. The amplitude of single postsynaptic potentials in the central nervous system is 1-5 mV. In a large neuromuscular synapse, an analogue of EPSP, the so-called end plate potential, reaches 40 mV or more . The time it takes to conduct excitation through the synaptic cleft is called synaptic delay. It is approximately 1 ms.

It is clear that in the overwhelming majority of cases (except for the end plate potential), a single EPSP is not capable of causing an AP. The excitation caused by the mediator simply does not reach the threshold level. Therefore, to achieve the PD triggering threshold, it is necessary summation(superposition) of several EPSPs. There are two options for summation - temporal and spatial. In the first case, there is a superposition of the effects of stimuli arriving at one synapse with a high frequency . Indeed, if a second, then a third, etc., is added to an EPSP that has not yet died out. – there will be a real opportunity to launch the PD. In real situations, this means that the signal reaching the synapse is intense enough and “deserves” to be transmitted further along the network of neurons. Spatial summation consists of superimposing EPSPs of neighboring synapses on each other in some region of the electrosensitive membrane adjacent to them. A membrane that has voltage-gated ion channels is called electrosensitive. A membrane possessing ligand-gated ion channels is called chemosensitive.

In the case of real neuronal activity, the effects of spatial and temporal summation are combined. And the more synapses participate in this process (that is, they fire relatively simultaneously), the greater the likelihood of reaching the threshold for triggering an action potential. In this case, some synapses may have inhibitory properties and cause IPSP. Consequently, their effects will be subtracted from the sum of the exciting influences. In general, as a first approximation, the condition for launching a PD at each moment of time can be determined as follows:

å EPSP - å IPSP ³ PD trigger threshold

However, assessing the contribution of specific postsynaptic potentials to this result is quite difficult. The fact is that their influence quickly fades away as they move away from the place of origin. In addition, attenuation in the processes occurs faster than in the body of the neuron, and the faster the thinner the process. Finally, the electrosensitive membrane of a neuron has slightly different excitability in different places. It is maximum in the axon hillock (the place where the axon departs from the neuron body) and in the places of the first branching of large dendrites. As a result, it turns out that the closer a particular synapse is to these points, the greater its contribution to controlling the generation of APs. One IPSP arising near the axon hillock may be sufficient to stop signal transmission.

The process of summing EPSPs and IPSPs that arise at different synapses is, in fact, the main computational operation that occurs on neurons of the central nervous system. When implemented, signals have the opportunity to “confirm” their significance, can combine with other signals and form some “information image”, can be blocked (in the presence of certain conditions - signals through inhibitory channels), etc. It follows from this that the most elementary structural and functional unit of the central nervous system is not a neuron, but a synapse. The ability of the central nervous system to perform complex computational operations is thus determined not by its total weight or even the number of neurons, but by the number of synapses. This amount in the human brain is apparently measured in tens of trillions. Moreover, as individual ontogenesis progresses, the brain is able to form additional synapses, increasing its potential. This process is especially intense in the early postnatal period, when the nervous system is adjusted to the upcoming level of information load.

So, information in the neural network is transmitted as follows: an excitatory (causing EPSP) transmitter is released from the presynaptic terminal, an AP occurs in the postsynaptic neuron, it spreads along the axon to its end, there the transmitter is released again, etc. Each newly formed PD is the same in size (the “all or nothing” law). As a result, the signal travels quickly and without attenuation.

However, the propagation of information in the nervous system must have some starting point. In this regard, the question arises: where does the first EPSP come from? The answer is this: it arises in special sensory formations that perceive influences from the external world or the internal environment of the body. As a result, changes in the permeability of cell membranes occur. They lead to the development of special receptor potentials, similar in properties to PSP, and ultimately to the generation of AP in the sensory nerve. Essentially, sensory formations of different types translate numerous forms of energy (chemical, mechanical, light, thermal) into a single language of nerve signals that the brain understands.

Nervous system mediators

Mediator life cycle

This and the following sections of this manual are devoted to the chemical aspects of the nervous system, a description of various mediator systems and psychotropic drugs. However, before moving on to specific substances that carry out and regulate synaptic transmission, the life cycle of a “generalized” transmitter should be considered. It includes the following stages: synthesis, loading into the vesicle and transport to the presynaptic terminal; release into the synaptic cleft; binding to a receptor on the postsynaptic membrane; inactivation.

The formation of the transmitter often occurs directly at the presynaptic terminal. This is possible when the synthesis process is chemically relatively simple and does not require any hard-to-find precursors. If these conditions are not met, the formation of a transmitter occurs in the body of the neuron. This is especially true for peptide mediators that arise as a result of “cutting” from larger protein molecules. The synthesis of each specific mediator is associated with specific enzymes that carry out the corresponding reactions. The activity of the mediator system ultimately depends on their quantity and activity.

The neurotransmitter molecules synthesized in the neuron body are transferred first to the endoplasmic reticulum and then to the Golgi apparatus. This organelle provides exocytosis of mediators, pre-packing them into membrane vesicles - vesicles. The resulting vesicles are transported to presynaptic terminals using fast axonal transport.

In the case when the transmitter is synthesized immediately at the presynaptic terminal, the Golgi apparatus is capable of forming empty vesicles. They are similarly transported along the axon. The filling of vesicles with mediator occurs directly at the presynaptic terminal (due to the work of special molecular pumps). The number of vesicles accumulating in the presynaptic terminal is measured in the thousands. Depletion of mediator reserves, even with intensive transmission of information, occurs very rarely (usually due to the action of special pharmacological agents).

Each neuron produces only one main transmitter (acetylcholine, dopamine, etc.). However, other substances capable of transmitting nerve signals can often be found in the presynaptic terminal. These are so-called comediators (for example, peptides). They are found in very small quantities and are usually found in vesicles that differ in shape and size from the vesicles containing the main transmitter.

The release of the contents of the vesicles is triggered at the moment the action potential arrives at the presynaptic terminal (Fig. 10). In this case, the electrical signal is essentially converted into a chemical one. Such a transformation is a rather complex task and is carried out in several stages. The first one is to open voltage-gated Ca 2+ channels.

Channels of this kind are widespread in the nervous system. In this case, they are located in the membrane of the presynaptic terminal and open during its depolarization, which is caused by the arrival of AP. As a result, a certain portion of Ca 2+ ions enters the cell, and their content inside the terminal increases 10-100 times. It is clear that the greater the concentration of Ca 2+ in the external environment, the greater will be the number of incoming ions.

The main purpose of Ca 2+ ions in the presynaptic terminal is to influence the complex protein complex embedded in the vesicle membrane. This complex includes proteins responsible for fixation (“anchoring”) of the vesicle in the cytoplasm of the presynaptic terminal and for its contact with the presynaptic membrane. Under the influence of Ca 2+ (it is assumed that this requires four ions), the vesicle begins to move. Reaching the presynaptic membrane, the vesicle “sticks” to it, as a result of which the transmitter enters the synaptic cleft. This whole process occurs very quickly - within 1-5 ms. Interestingly, after about 10 s, the process of vesicle restoration can be observed: they are separated from the presynaptic membrane and returned to the presynaptic terminal. In the future, these empty bubbles can be filled again with a mediator.

Interestingly, Mg 2+ ions are also able to penetrate through calcium channels, competing with calcium. Consequently, the appearance of magnesium in the intercellular environment reduces the total amount of calcium entering the terminal. Therefore, the introduction of a large amount of Mg 2+ (for example, in the form of magnesium - MgSo 4) leads to a decrease in the release of the transmitter and, consequently, to a weakening of synaptic signal transmission.

Once in the synaptic cleft, the transmitter interacts with specialized protein receptors built into the presynaptic membrane in less than 1 ms. The spatial organization of such a receptor provides for the existence of an “active center” - a site in a protein molecule that has a certain shape and charge distribution. This region strictly corresponds to the spatial configuration of the mediator and the distribution of charges on its molecule. The active center of the receptor and the mediator are able to form a complex (according to the “key to the lock” principle). The immediate consequence of this is the activation of the receptor, and the relatively distant consequence is the development of postsynaptic potentials and the initiation of action potentials.

Contact between a transmitter and a receptor can lead to different consequences depending on what type of particular receptor belongs to. In the most general case, there are two types of these receptors: ionotropic and metabotropic receptors.

Activation metabotropic receptor(Fig. 11) leads to changes in intracellular metabolism, that is, the course of some biochemical reactions. On the inner side of the membrane, a number of other proteins are attached to such a receptor, partly performing enzymatic, partly transmitting (“intermediary”) functions. Mediator proteins belong to the group of G proteins. Under the influence of an activated receptor, the G protein acts on the enzyme protein, transferring it to an active “working” state. This means that a certain chemical reaction is started. Its essence is that a certain precursor molecule is converted into a signaling molecule - a second messenger.

Secondary intermediaries- these are small molecules or ions capable of rapid movement that transmit a signal inside the cell. This is how they differ from “primary messengers” – mediators and hormones that transmit information from cell to cell. The best known second messenger is cAMP (cyclic adenosine monophosphoric acid), formed from ATP by the enzyme adenylate cyclase. Similar to it is cGMP (guanosine-mono-phosphoric acid). Other important second messengers are inositol triphosphate and diacylglycerol, formed from components of the cell membrane. The role of Ca 2+, which enters the cell from the outside through ion channels or is released from special storage sites inside the cell (calcium “depot”), is extremely important. Recently, much attention has been paid to the very short-lived second messenger NO (nitric oxide). It has been shown that NO is capable of transmitting a signal not only within a cell, but also between cells (including from a postsynaptic neuron to a presynaptic one).

The final step in chemical signal transduction is the action of the second messenger on the chemosensitive ion channel. This effect occurs either directly or through additional intermediate links (for example, enzymes). In any case, the ion channel opens and an EPSP or IPSP develops. The duration and amplitude of their first phase will be determined by the amount of the secondary messenger, which, in turn, depends on the amount of the released mediator and the duration of its interaction with the receptor.

Thus, the mechanism of nerve stimulus transmission used by metabotropic receptors includes several successive stages. At each of them, regulation (weakening or strengthening) of the signal is possible, which makes the reaction of the postsynaptic cell more flexible and adapted to current conditions. At the same time, this also leads to a slowdown in the process of information transfer. That is why, during the course of evolution, the need arose for a faster signal pathway, resulting in the emergence of ionotropic receptors.

In the case of an ionotropic receptor (see Fig. 13), the sensitive molecule contains not only an active site for binding the mediator, but also an ion channel. The effect of the mediator on the receptor leads to almost instantaneous opening of the channel and the development of the postsynaptic potential. For example, neuromuscular synapses work on this principle.

Inactivation is the final stage of the mediator life cycle. The meaning of this stage is to stop its action on the receptor (interruption of the signal). Indeed, APs propagating along the membrane of nerve cells are discrete, time-limited events. For adequate signal transmission from neuron to neuron, this discreteness must be preserved. Accordingly, synaptic transmission must also be limited in time and have mechanisms not only for initiation, but also for termination.

In the simplest case, inactivation occurs directly at the synaptic target. In this case, the enzyme effectively destroys all free-floating mediator molecules. Of course, some of them still manage to reach the postsynaptic membrane. However, their connection with the active centers of the receptors is not absolutely stable. The point is that the ligand-receptor interaction is usually probabilistic. This means that in reality the transmitter molecule is in connection with the active center, say, 2/3 of the time, but 1/3 is freely floating in the synaptic cleft. It is at this moment that it can be inactivated.

The second method of inactivation involves the absorption of the transmitter from the synaptic cleft using special pump proteins. These proteins can be located either on the membranes of glial cells or on the presynaptic membrane. In the first case, the mediator is quickly transferred inside glial cells, after which it is destroyed by a specialized enzyme. In the second case, the transmitter returns to the presynaptic terminal ( recapture). In the future, it can also be destroyed, but it can also be reloaded into empty vesicles. The latter option allows the most economical use of those mediators whose synthesis is associated with certain problems for the neuron (little precursor, long chain of reactions, etc.).

The rate of the inactivation process determines the total time of exposure of the mediator to the receptor. It is on this that the amplitude of postsynaptic potentials ultimately depends, and, therefore, the initiation of APs and the continuation of signal transmission through the neural network. When elements of the inactivation system are damaged, we observe a significant increase in the efficiency of synaptic transmission. Indeed, in this case, the released transmitter will act on the receptors for a much longer time, and the amplitude of the EPSP or IPSP will noticeably increase.

All neurons are divided into types depending on the transmitter they produce. In this case, “-ergic” is added to the name of the mediator. Thus, acetylcholinergic neurons that synthesize acetylcholine form the acetylcholinergic system, neurons that synthesize glutamic acid form the glutamatergic system, etc.

A neuron can be connected to neurons of both its transmitter system and other systems. The matter is complicated by the fact that, as a rule, there is not one type of receptor for one mediator, but two or more, and for one mediator there can be both ionotropic and metabotropic receptors.

Substances that influence various stages of the life cycle of mediators are of great importance for human life. They form a group of so-called psychotropic drugs– compounds that affect various aspects of brain activity: the general level of activity, memory, emotional experiences, etc. In this case, the most commonly used substances are those that change the interaction between the receptor and the mediator, as well as those that affect chemosensitive ion channels.

By introducing molecules into the body that are similar in structure to the mediator, one can observe how they connect with the active centers of the corresponding receptors and excite them. As a result, the effect of the drug used will be similar to the effect of the mediator itself. Substances of this kind are called agonists mediator. The effect of agonists on the synapse is often very long-lasting and effective. This is explained by the fact that the strength of their binding to receptors is often greater than that of the mediator, and inactivation systems are not able to quickly remove the agonist from the synaptic cleft.

In a more complex case, molecules introduced from the outside are only partially similar to the mediator. Then, connecting with the active centers of the receptors, they will occupy them (i.e., stop the mediator from accessing them; compete with it), but will not excite the receptor. As a result, the effect of the drug used will be opposite to the effect of the mediator. Substances of this kind are called competitive antagonists(blockers) of the mediator. There is also the concept of a non-competitive antagonist. In this embodiment, the administered drug disrupts the action of the mediator by blocking chemosensitive ion channels.

Some agonists and antagonists of mediators are substances of natural origin. Their existence is the result of long evolutionary processes, during which some living organisms (primarily plants) “invented” substances that protected them from being eaten by other organisms. Poisons from hunting animals (snakes, spiders, etc.) are also natural psychotropic drugs.

The second part of agonists and antagonists are synthetic compounds created by humans. During their development, chemists and pharmacologists have to take into account a number of requirements. Firstly, the structure of such a substance must contain a “key” region corresponding to the mediator molecule. Secondly, such a drug must be resistant to inactivation systems. Thirdly, it must penetrate the body’s barriers - blood-brain and, preferably, intestinal. Only in this case can it reach the brain when introduced into the body in the form of a tablet or injection. Currently, agonists and antagonists of neurotransmitters (as well as compounds that affect synaptic transmission in other ways) are widely used in the clinic. At the same time, in large doses, many of them are drugs and poisons, which also indicates the need for their serious study.

Mediators are very diverse in their chemical structure. In this regard, among them there are groups of monoamines (derivatives of amino acids), amino acids, peptides (chains of amino acids). Acetylcholine has a peculiar chemical nature, with which we will begin our review of the main mediator systems and the psychotropic drugs associated with them.

Acetylcholine

Acetylcholine was the first neurotransmitter to be discovered. According to its chemical structure, it is a combination of two molecules - nitrogen-containing choline and an acetic acid residue. Acetylcholine synthesis occurs mainly in presynaptic terminals using the enzyme choline acetyltransferase. The transmitter is then transferred into empty vesicles and stored there until released.

Acetylcholine acts as a mediator in three functional blocks of the nervous system. These are neuromuscular synapses, the peripheral part of the autonomic nervous system and relatively few areas of the central nervous system.

Acetylcholine is a transmitter of motor neurons of the nervous system, localized in the anterior horns of the gray matter of the spinal cord and the motor nuclei of the cranial nerves. Their axons are directed to the skeletal muscles and, branching, form neuromuscular synapses with them. In this case, one axon can establish contact with 5-5000 muscle fibers; but each muscle fiber is controlled by only one synapse. The size of neuromuscular synapses is tens of times larger than synapses in the central nervous system. Even a single AP arriving along the axon of a motor neuron causes the release of a very significant amount of acetylcholine at the synapse. As a result, the depolarization developing on the postsynaptic membrane is so great that it always triggers the action of the muscle cell. This AP, in turn, leads to the release of Ca 2+ from the endoplasmic reticulum channels, activation of motor proteins and contraction of the striated fiber.

In the autonomic nervous system, acetylcholine as a mediator is produced by neurons located in the central nervous system, as well as in the ganglion cells of the parasympathetic part. Consequently, with the help of this mediator, signals are transmitted within the autonomic ganglia, as well as parasympathetic influences directly on the internal organs.

In the central nervous system, acetylcholine is produced by part of the neurons of the reticular nuclei of the pons, interneurons of the basal ganglia (more precisely, the striatum) and some other local zones. The role of this mediator in the regulation of the level of wakefulness, memory systems, and motor systems is considered.

Released from the presynaptic terminal, acetylcholine acts on postsynaptic receptors. These receptors are not homogeneous and differ both in location and in a number of essential properties. There are two types of them, named after their agonists. The first type, in addition to acetylcholine, is excited by the action of the tobacco alkaloid nicotine (nicotinic receptors or H-cholinergic receptors). The second type is activated by acetylcholine and the fly agaric toxin muscarine (muscarinic receptors or M-cholinergic receptors). Let's take a closer look at them.

Nicotinic receptors are a classic example of ionotropic receptors, i.e. their ion channel is part of the receptor and opens immediately after the addition of acetylcholine. This channel is characterized by universal permeability for positively charged ions. However, under normal conditions (when opening against the background of PP), mainly incoming Na + current is observed through their channels, causing depolarization of the membrane and excitation of the neuron.

N-cholinergic receptors are located on the postsynaptic membrane of striated fibers of skeletal muscles (neuromuscular synapses), in the synapses of the autonomic ganglia, and in smaller numbers than muscarinic receptors in the central nervous system. The area most sensitive to nicotine is the autonomic ganglia (especially the sympathetic ones). Therefore, the first attempts at smoking lead to significant disturbances in the functioning of internal organs, surges in blood pressure, nausea, etc. As one gets used to it, the sympathetic component of the action is mainly retained - i.e. Nicotine begins to work primarily as a stimulant for many body systems. There is also a central (on the brain) activating effect of acetylcholine. Overdoses of nicotine (50 mg or more) cause a sharp increase in heart rate, convulsions and respiratory arrest.

When used during smoking as a weak narcotic stimulant, nicotine causes the development of not only addiction, but also dependence - a situation when the body includes a drug coming from outside into its metabolism, i.e. “counts” on its constant influx. When you stop taking the drug, a disruption occurs in the brain systems that use it. As a result, there is a sharp deterioration in well-being, depression, etc. (withdrawal syndrome or withdrawal syndrome). Thus, a person who has become addicted needs a drug not so much to feel cheerfulness and euphoria, but to return at least to a relatively “normal” level of functioning.

The most well-known antagonist of nicotinic receptors is d-tubocurarine, the active principle of a poison prepared from some South American plants. Its main site of application is neuromuscular synapses. In this case, there is a sequential relaxation of the muscles of the fingers, then the eyes, arms and legs, neck, back and, finally, the respiratory muscles. The duration of action of d-tubocurarine is relatively short - 30-60 minutes. If you maintain artificial respiration all this time, then after the end of the tubocurarine action there will be no significant damage to the body.

Snake neurotoxins have an even stronger effect on the neuromuscular junction. For example, cobra venom contains a-neurotoxin, which almost irreversibly binds to the nicotinic receptor and blocks it. The venom also contains b-neurotoxin, which inhibits the release of the transmitter from the presynaptic ending.

Antagonists of nicotinic receptors in the brain, cyclodol and akineton, are used to reduce the symptoms of parkinsonism. Their introduction reduces the manifestations of motor disorders characteristic of this disease.

Muscarinic receptors are metabotropic. They are associated with G proteins, and the addition of acetylcholine to them leads to the synthesis of second messengers.

These receptors are found both in the central nervous system and in the periphery, where they are located on the target organs of the parasympathetic nervous system. The ionic consequences of excitation of muscarinic receptors are very diverse. Thus, in the heart there is an increase in conductivity for K + ions, which leads to hyperpolarization and a decrease in the frequency of contractions. In the case of smooth muscles, changes in conductivity are noted for both K + and Na +; Accordingly, hyper- or depolarization is possible, depending on the specific organ.

In the central nervous system there is a decrease in conductivity for K + (depolarization, excitatory effect). At the same time, synapses containing muscarinic receptors can be located on both inhibitory and excitatory neurons of the cortex, basal ganglia, etc. In this regard, the consequences of blockade or activation of muscarinic receptors at the behavioral level are very individual.

In the peripheral nervous system, the effects of muscarine are predominantly parasympathetic. In case of fly agaric poisoning, nausea, increased sweating and salivation, lacrimation, abdominal pain, decreased blood pressure and cardiac activity are observed. The amount of muscarine that causes coma and death is 0.5 g.

The classic antagonist of muscarinic receptors is atropine, an alkaloid of henbane and datura. Its peripheral effects are exactly the opposite of those of muscarine. Under the influence of atropine, the muscle tone of the gastrointestinal tract decreases, the heart rate increases, and salivation stops (“dry mouth”). Dilation of the pupils is extremely characteristic. Central (mediated through the central nervous system) effects are also observed: motor and speech excitation, hallucinations.

At the same time, a number of muscarinic receptor antagonists have a calming effect. For example, a drug such as amizil is classified as a tranquilizer and is used for movement disorders.

Inactivation of acetylcholine occurs directly in the synaptic cleft. It is carried out by an enzyme acetylcholinesterase, decomposing the mediator to choline and acetic acid residue. Subsequently, choline is absorbed into the presynaptic terminal and can again be used for the synthesis of acetylcholine.

Acetylcholinesterase has an active site that recognizes choline and another active site that abstracts an acetyl group from the parent molecule. It is the latter that is most often the site of attack by specific blockers. An example is eserine (physostigmine), an alkaloid of one of the types of African legumes that causes constriction of the pupil, drooling, and slowing of the heart rate.

A synthetic analogue of eserine is proserine (neostigmine), used for myasthenia gravis. Its symptoms include rapid muscle fatigue, involuntary drooping of the eyelids, and slow chewing. The introduction of acetylcholinesterase blockers weakens the pathological manifestations. It has been shown that in a significant proportion of patients with myasthenia gravis, the number of nicotinic receptors is approximately 70% less than normal. The reason for this is that the patient's immune system produces antibodies to nicotinic receptors. These antibodies accelerate the destruction of receptors on the membrane, weakening transmission at the neuromuscular junction. Diseases of this kind are called autoimmune.

Prozerin and similar drugs are called reversible acetylcholinesterase blockers, and their effect ceases a few hours after administration. In addition, there are irreversible blockers of the same enzyme. In this case, the substance that disrupts the functioning of acetylcholinesterase enters into a stable chemical bond with the protein and disables it. Such blocking agents are various nerve gases (sarin, etc.). Easily penetrating all body barriers, they cause convulsions, loss of consciousness and paralysis. Death occurs from respiratory arrest. To immediately reduce the effects of gases, the use of atropine is recommended; to restore the activity of acetylcholinesterase - special reactivating substances that separate the blocker from the enzyme.

Monoamines

Monoamine mediators include catecholamines, serotonin and histamine. All of them are derivatives of various amino acids.

Catecholamines

Catecholamines include three neurotransmitters: norepinephrine, adrenaline and dopamine. All of them are formed from the amino acid tyrosine - an essential amino acid that we get only from food.

Tyrosine ® L-DOPA ® dopamine ® norepinephrine ® adrenaline

The key, slowest step is the first reaction of converting tyrosine into L-DOPA (dioxyphenylalanine). And the enzyme that catalyzes this reaction, tyrosine hydroxylase, is of particular importance. The synthesis of catecholamines occurs mainly in presynaptic terminals. They are then transferred into empty vesicles, where they are stored until released.

Norepinephrine

Catecholamine adrenalin is an adrenal hormone. Norepinephrine plays an important role in both the central and peripheral nervous systems as a mediator.

In the periphery, norepinephrine is a transmitter at most postganglionic synapses of the sympathetic nervous system. By acting on internal organs, it has an effect opposite to acetylcholine.

Released from the presynaptic terminal, norepinephrine acts on postsynaptic receptors. These receptors are divided into two types, which are called alpha and beta adrenergic receptors. Both of them are metabotropic. The difference is that alpha adrenergic receptors use inositol triphosphate, diacylglycerol and Ca 2+ ions as second messengers. Beta-adrenergic receptors are connected to the enzyme adenylate cyclase, which is involved in the synthesis of cyclic adenosine monophosphate (cAMP). It was the study of beta-adrenergic receptors that made it possible for the first time to identify the existence of a system of second messengers and describe its main properties. The consequence of activation of adrenergic receptors can be a change in both sodium and potassium conductivity - that is, excitatory or inhibitory effects depending on the specific location of the receptors.

The classic alpha-adrenergic receptor agonist is the drug fethanol, and the antagonist is phentolamine. In the case of beta-adrenergic receptors, the most well-known agonist isadrin and antagonist propranolol (synonyms - anaprilin, obzidan).

Each internal organ contains either alpha or beta adrenergic receptors, or both types.

The figure shows a neuron in the state resting and unexcited presynaptic terminal in contact with its surface. The resting membrane potential throughout the soma is -65 mV.

The picture shows presynaptic terminal from which the excitatory transmitter was released into the gap between the terminal and the membrane of the neuron soma. This transmitter acts on the membrane excitatory receptor, increasing the permeability of the membrane to Na+. Due to the large concentration gradient of Na+ ions and significant electronegativity inside the neuron, Na+ ions quickly diffuse into the cell.

Rapid influx positively charged Na+ ions inside the cell partially neutralizes the negativity of the resting membrane potential. Thus, in the figure, the resting membrane potential has shifted in the positive direction from -65 to -45 mV. This positive shift in the resting membrane potential is called the excitatory postsynaptic potential (EPSP), because if this potential shifts significantly in the positive direction, it leads to the development of an action potential in the postsynaptic neuron, i.e. to his excitement. (In this case, the EPSP is +20 mV, i.e., the membrane potential has become 20 mV more positive than at rest.)

However, the following should be noted. Singles one presynaptic terminal will never be able to increase the neuron potential from -65 mV immediately to -45 mV. Such a large potential shift requires the discharge of many terminals (approximately 40-80 for a typical spinal motor neuron) simultaneously or in rapid succession. This involves a process called summation, which is detailed in the following articles.
Generation of action potentials in the initial segment of the axon extending from the neuron body. Excitation threshold.

When the EPSP shifts quite strongly in the positive direction, a level of depolarization is reached at which an action potential develops in the neuron. However, the action potential does not arise in the part of the membrane adjacent to the excitatory synapses, but in the initial segment of the axon - at the point of transition of the neuron soma into the axon.

The main reason This is due to the relatively small number of voltage-gated sodium channels in the soma membrane of the neuron, which, during the development of EPSP, makes it difficult to open the required number of sodium channels for the occurrence of an action potential.

Vice versa, concentration of voltage-gated sodium channels in the membrane of the initial segment is 7 times more than in the membrane of the soma, and, therefore, this region of the neuron can generate an action potential much more easily than the soma. The EPSP capable of eliciting an action potential at the axon initial segment ranges between +10 and +20 mV (compared to +30 or +40 mV or more required to excite the soma).

Immediately after action potential develops, it extends along the axon to the periphery and usually also to the soma. In some cases it extends into the dendrites, but not all, since they, like the neuron soma, have very few voltage-gated sodium channels and therefore often fail to generate action potentials.

The figure shows that neuron excitation threshold equal to approximately -45 mV, i.e. 20 mV more positive than the neuron's resting potential of -65 mV, corresponding to an EPSP of +20 mV.

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The mediator quanta released through the presynaptic membrane diffuse through the synaptic cleft to the postsynaptic membrane, where they bind to special chemical cellular receptors specific to the mediator molecules. The “mediator-receptor” complex formed on the postsynaptic membrane activates chemosensitive membrane channels, which increases the permeability of the membrane to ions and changes its resting potential. In the absence of excitation pulses, these short-term permeability shifts form very small amplitude peaks, called miniature postsynaptic potentials, occurring at variable time intervals (on average about 1 s), but always of the same amplitude. Consequently, miniature potentials are the result of spontaneous, random release of single quanta of the mediator. When a nerve impulse arrives at the presynaltic membrane, the number of quanta of the released transmitter increases sharply, and many “transmitter-receptor” complexes are simultaneously formed, participating in the generation of the postsynaptic potential.

Excitatory postsynaptic potential

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In excitatory synapses of the nervous system, the mediator can be acetylcholine, norepinephrine, dopamine, serotonin, glugamic acid, substance P, as well as a large group of other substances that are, if not mediators in the direct sense, then at least modulators (changing the effectiveness) of synaptic transmission. Excitatory mediators cause the appearance on the postsynaptic membrane excitatory postsynaptic potential(EPSP). Its formation is due to the fact that the mediator-receptor complex activates Na-channels of the membrane (and probably also Ca-channels) and causes depolarization of the membrane due to the entry of sodium into the cell. At the same time, there is a decrease in the release of K+ ions from the cell. The amplitude of a single EPSP, however, is quite small, and to reduce the membrane charge to a critical level of depolarization, simultaneous activation of several excitatory synapses is necessary.

EPSPs formed on the postsynaptic membrane of these synapses are capable of totalto hang out, those. reinforce each other, leading to an increase in EPSP amplitude (spatial summation).

The amplitude of EPSP also increases with an increase in the frequency of nerve impulses arriving at the synapse (time variable summation), which increases the number of transmitter quanta released into the synaptic cleft.

The process of spontaneous regenerative depolarization occurs in a neuron, usually at the point where the axon departs from the cell body, in the so-called axon hillock, where the axon is not yet covered with myelin and the excitation threshold is lowest. Thus, EPSPs arising in different parts of the neuron membrane and on its dendrites propagate to the axon hillock, where they are summed up, depolarizing the membrane to a critical level and leading to the appearance of an action potential.

Inhibitory postsynaptic potential

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At inhibitory synapses, other inhibitory neurotransmitters usually act. Among them, the amino acid glycine (inhibitory synapses of the spinal cord) and gamma-aminobutyric acid (GABA), an inhibitory transmitter in brain neurons, are well studied. At the same time, an inhibitory synapse may have the same transmitter as the excitatory one, but the nature of the receptors on the postsynaptic membrane is different. Thus, for acetylcholine, biogenic amines and amino acids, at least two types of receptors can exist on the postsynaptic membrane of different synapses, and, therefore, different transmitter-receptor complexes can cause different reactions of chemosensitive receptor-gated channels. For an inhibitory effect, such a reaction may be the activation of potassium channels, which causes an increase in the release of potassium ions out and hyperpolarization of the membrane. A similar effect in many inhibitory synapses is the activation of chlorine channels, increasing its transport into the cell. The shift in membrane potential that occurs during hyperpolarization is called brakeno postsynaptic potential(TPSP). Figure 3.5 shows the distinctive features of EPSP and IPSP. An increase in the frequency of nerve impulses arriving at the inhibitory synapse, as well as at excitatory synapses, causes an increase in the number of inhibitory transmitter quanta released into the synaptic cleft, which, accordingly, increases the amplitude of the hyperpolarizing IPSP. At the same time, IPSP is not able to spread across the membrane and exists only locally.

As a result of IPSP, the level of membrane potential moves away from the critical level of depolarization and excitation either becomes impossible at all, or excitation requires the summation of EPSPs that are significantly larger in amplitude, i.e. the presence of significantly larger exciting currents. With the simultaneous activation of excitatory and inhibitory synapses, the EPSP amplitude sharply decreases, since the depolarizing flow of Na + ions is compensated by the simultaneous release of K + ions in some types of inhibitory synapses or the input of SG ions in others, which is called bypass EPSP.

Fig.3.5. Excitatory (B) and inhibitory (T) synapses and their potentials.

RMP - resting membrane potential.
Arrows at synapses show the direction of current.

Under the influence of certain poisons, blockade of inhibitory synapses in the nervous system can occur, which causes uncontrollable excitation of numerous reflex apparatuses and manifests itself in the form of convulsions. This is how strychnine acts by competitively binding to the receptors of the postsynaptic membrane and preventing them from interacting with the inhibitory transmitter. Tetanus toxin, which disrupts the release of the inhibitory transmitter, also inhibits inhibitory synapses.

It is important to distinguish between two types of inhibition in the nervous system: primary and secondary

In excitatory synapses of the nervous system, the mediator can be acetylcholine, norepinephrine, dopamine, serotonin, glugamic acid, substance P, as well as a large group of other substances that are, if not mediators in the direct sense, then at least modulators (changing the effectiveness) of synaptic transmission. Excitatory mediators cause the appearance on the postsynaptic membrane excitatory postsynaptic potential(EPSP). Its formation is due to the fact that the mediator-receptor complex activates Na-channels of the membrane (and probably also Ca-channels) and causes depolarization of the membrane due to the entry of sodium into the cell. At the same time, there is a decrease in the output of K + ions from the cell. The amplitude of a single EPSP, however, is quite small, and to reduce the membrane charge to a critical level of depolarization, simultaneous activation of several excitatory synapses is necessary.

EPSPs formed on the postsynaptic membrane of these synapses are capable of add up, those. reinforce each other, leading to an increase in EPSP amplitude (spatial summation).

The amplitude of EPSP also increases with an increase in the frequency of nerve impulses arriving at the synapse (time summation), which increases the number of transmitter quanta released into the synaptic cleft.

The process of spontaneous regenerative depolarization occurs in a neuron, usually at the point where the axon departs from the cell body, in the so-called axon hillock, where the axon is not yet covered with myelin and the excitation threshold is lowest. Thus, EPSPs arising in different parts of the neuron membrane and on its dendrites propagate to the axon hillock, where they are summed up, depolarizing the membrane to a critical level and leading to the appearance of an action potential.

Inhibitory postsynaptic potential (IPSP) At inhibitory synapses, other inhibitory neurotransmitters usually act. Among them, the amino acid glycine (inhibitory synapses of the spinal cord) and gamma-aminobutyric acid (GABA), an inhibitory transmitter in brain neurons, are well studied. At the same time, an inhibitory synapse may have the same transmitter as the excitatory one, but the nature of the receptors on the postsynaptic membrane is different. Thus, for acetylcholine, biogenic amines and amino acids, at least two types of receptors can exist on the postsynaptic membrane of different synapses, and, therefore, different transmitter-receptor complexes can cause different reactions of chemosensitive receptor-controlled channels. For an inhibitory effect, such a reaction may be the activation of potassium channels, which causes an increase in the release of potassium ions out and hyperpolarization of the membrane. A similar effect in many inhibitory synapses is the activation of chlorine channels, increasing its transport into the cell. The shift in membrane potential that occurs during hyperpolarization is called inhibitory postsynaptic potential(TPSP). Figure 3.5 shows the distinctive features of EPSP and IPSP. An increase in the frequency of nerve impulses arriving at the inhibitory synapse, as well as at excitatory synapses, causes an increase in the number of inhibitory transmitter quanta released into the synaptic cleft, which, accordingly, increases the amplitude of the hyperpolarizing IPSP. At the same time, IPSP is not able to spread across the membrane and exists only locally.


As a result of IPSP, the level of membrane potential moves away from the critical level of depolarization and excitation either becomes impossible at all, or excitation requires the summation of EPSPs that are significantly larger in amplitude, i.e. the presence of significantly larger exciting currents. With the simultaneous activation of excitatory and inhibitory synapses, the EPSP amplitude sharply decreases, since the depolarizing flow of Na + ions is compensated by the simultaneous release of K + ions in some types of inhibitory synapses or the input of SG ions in others, which is called bypass EPSP.

Under the influence of certain poisons, blockade of inhibitory synapses in the nervous system can occur, which causes uncontrollable excitation of numerous reflex apparatuses and manifests itself in the form of convulsions. This is how strychnine acts by competitively binding to the receptors of the postsynaptic membrane and preventing them from interacting with the inhibitory transmitter. Tetanus toxin, which disrupts the release of the inhibitory transmitter, also inhibits inhibitory synapses.

It is customary to distinguish between two types of inhibition in the nervous system: primary and secondary

All features of the spread of excitation in the central nervous system are explained by its neural structure: the presence of chemical synapses, multiple branching of neuron axons, and the presence of closed neural pathways. These features are the following.

1. Irradiation (divergence) of excitation in the central nervous system. It is explained by the branching of neuron axons, their ability to establish numerous connections with other neurons, and the presence of interneurons, the axons of which also branch (Fig. 4.4, a).

The irradiation of excitation can be observed in an experiment on a spinal frog, when weak stimulation causes flexion of one limb, and strong stimulation causes energetic movements of all limbs and even the torso. Divergence expands the scope of each neuron. One neuron, sending impulses to the cerebral cortex, can participate in the excitation of up to 5000 neurons.

Rice. 4.4. Divergence of afferent dorsal roots onto spinal neurons, the axons of which, in turn, branch, forming numerous collaterals (c), and convergence of efferent pathways from various parts of the central nervous system onto the α-motoneuron of the spinal cord (6)

1. Convergence of excitation (the principle of a common final path) - the convergence of excitation of different origins along several paths to the same neuron or neural pool (the Sherrington funnel principle). The convergence of excitation is explained by the presence of many axon collaterals, interneurons, and also by the fact that there are several times more afferent pathways than efferent neurons. One CNS neuron can have up to 10,000 synapses. The phenomenon of convergence of excitation in the central nervous system is widespread. An example is the convergence of excitation on a spinal motor neuron. Thus, primary afferent fibers (Fig. 4.4, b), as well as various descending pathways of many overlying centers of the brain stem and other parts of the central nervous system, approach the same spinal motor neuron. The phenomenon of convergence is very important: it ensures, for example, the participation of one motor neuron in several different reactions. The motor neuron innervating the muscles of the pharynx is involved in the reflexes of swallowing, coughing, sucking, sneezing and breathing, forming a common final pathway for numerous reflex arcs. In Fig. 4.4, I show two afferent fibers, each of which sends collaterals to 4 neurons in such a way that 3 neurons out of a total of 5 form connections with both afferent fibers. On each of these 3 neurons, two afferent fibers converge.

Many axonal collaterals, up to 10,000-20,000, can converge on one motor neuron, so the generation of AP at each moment depends on the total sum of excitatory and inhibitory synaptic influences. PDs occur only if excitatory influences predominate. Convergence can facilitate the process of emergence of excitation on common neurons as a result of spatial summation of subthreshold EPSPs or block it due to the predominance of inhibitory influences (see section 4.8).

3. Circulation of excitation along closed neural circuits. It can last for minutes or even hours (Fig. 4.5).

Rice. 4.5. Circulation of excitation in closed neural circuits according to Lorento de No (a) and according to I.S. Beritov (b). 1,2,3- excitatory neurons

Excitation circulation is one of the causes of the aftereffect phenomenon, which will be discussed further (see section 4.7). It is believed that the circulation of excitation in closed neural circuits is the most likely mechanism for the phenomenon of short-term memory (see section 6.6). Circulation of excitation is possible in a chain of neurons and within one neuron as a result of contacts of the branches of its axon with its own dendrites and body.

4. One-sided propagation of excitation in neural circuits and reflex arcs. The propagation of excitation from the axon of one neuron to the body or dendrites of another neuron, but not vice versa, is explained by the properties of chemical synapses, which conduct excitation in only one direction (see section 4.3.3).

5. The slow spread of excitation in the central nervous system compared to its spread along the nerve fiber is explained by the presence of many chemical synapses along the paths of excitation propagation. The time it takes for excitation to pass through the synapse is spent on the release of the transmitter into the synaptic cleft, its propagation to the postsynaptic membrane, the occurrence of EPSP and, finally, AP. The total delay in the transmission of excitation at the synapse reaches approximately 2 ms. The more synapses in a neuronal chain, the lower the overall speed of excitation propagation along it. Using the latent time of the reflex, or more precisely, the central time of the reflex, you can roughly calculate the number of neurons in a particular reflex arc.

6. The spread of excitation in the central nervous system is easily blocked by certain pharmacological drugs, which is widely used in clinical practice. Under physiological conditions, restrictions on the spread of excitation throughout the central nervous system are associated with the activation of neurophysiological mechanisms of neuronal inhibition.

The considered features of the propagation of excitation make it possible to approach the understanding of the properties of nerve centers.

4. MODERN CONCEPTS ABOUT THE FORMS AND MECHANISMS OF INHIBITION IN THE CNS. FUNCTIONAL SIGNIFICANCE OF DIFFERENT FORMS OF BRAKING.

Braking in the central nervous system is the process of weakening or stopping the transmission of nerve impulses. Inhibition limits the spread of excitation (irradiation) and allows for fine regulation of the activity of individual neurons and the transmission of signals between them. Most often, inhibitory neurons are interneurons. It is thanks to the interaction of the processes of excitation and inhibition in the central nervous system that the activities of individual body systems are combined into a single whole (integration) and the coordination and coordination of their activities is carried out. For example, concentration of attention can be considered as a weakening of irradiation and strengthening of induction. This process improves with age. The importance of inhibition also lies in the fact that from all sensory organs, from all receptors, a continuous flow of signals flows into the brain, but the brain does not react to everything, but only to the most significant at the moment. Inhibition allows you to more accurately coordinate the work of different organs and systems of the body. With the help of presynaptic inhibition, the flow of certain types of nerve impulses to the nerve centers is limited. Postsynaptic inhibition weakens reflex reactions that are currently unnecessary or unimportant. It underlies, for example, the coordination of muscle work.

There are primary and secondary inhibition. Primary inhibition develops primarily without prior excitation and manifests itself in hyperpolarization of the neuronal membrane under the action of inhibitory neurotransmitters. For example, reciprocal inhibition under the action of inhibitory neurotransmitters. Primary inhibition includes presynaptic and postsynaptic inhibition, secondary inhibition includes pessimal and inhibition following excitation. Secondary braking occurs without the participation of special inhibitory structures, as a consequence of excessive activation of excitatory neurons (Vvedensky inhibition). It plays a protective role. Secondary inhibition is expressed in persistent depolarization of neuronal membranes, exceeding a critical level and causing inactivation of sodium channels. Central inhibition (I.M. Sechenov) is inhibition caused by excitation and manifested in the suppression of other excitation.

Braking classification:

I. By localization of the site of application in the synapse:

1 – presynaptic inhibition– observed in axo-axonal synapses, blocking the spread of excitation along the axon (in the structures of the brain stem, in the spinal cord). In the area of ​​contact, an inhibitory transmitter (GABA) is released, causing hyperpolarization, which disrupts the conduction of the excitation wave through this area.

2 – postsynaptic inhibition– the main type of inhibition, develops on the postsynaptic membrane of axosomatic and axodendritic synapses under the influence of released GABA or glycine. The action of the mediator causes a hyperpolarization effect in the postsynaptic membrane in the form of IPSP, which leads to a decrease or complete cessation of AP generation.

II. By effects in neural circuits and reflex arcs:

1 – reciprocal inhibition – carried out to coordinate the activity of muscles that are opposite in function (Sherrington). For example, the signal from the muscle spindle comes from the afferent neuron to the spinal cord, where it switches to the flexor α-motoneuron and at the same time to the inhibitory neuron, which inhibits the activity of the extensor α-motoneuron.

2 – return braking– is carried out to limit excessive excitation of the neuron. For example, an α-motoneuron sends an axon to the corresponding muscle fibers. Along the way, a collateral departs from the axon and returns to the central nervous system - it ends at the inhibitory neuron (Renshaw cell) and activates it. The inhibitory neuron causes inhibition of the α-motoneuron, which launched this entire chain, that is, the α-motoneuron inhibits itself through the inhibitory neuron system.

3 – lateral inhibition(return option). Example: a photoreceptor activates a bipolar cell and at the same time a nearby inhibitory neuron, which blocks the conduction of excitation from the neighboring photoreceptor to the ganglion cell (“information inhibition.”

III. According to the chemical nature of the neurotransmitter:

1 – GABAergic,

2 – glycinergic,

3 – mixed.

IV. Classification of types of braking according to I.P. Pavlov(Table 1)

Table 1 – Types of braking (according to I.P. Pavlov)

Braking type Type of braking Characteristic Biological significance
Unconditional inhibition External Distraction by unexpected new stimuli Change of dominant, switching to collecting new information
Transcendent Result of fatigue “Protective”, protecting the nervous system from damage
Conditional Fading Weakening of the response when the conditioned stimulus is not reinforced Refusal of ineffective behavioral programs, forgetting unused programs
Differentiation Cessation of a reaction to a stimulus similar to the conditioned one, but not reinforced Subtle discrimination of similar sensory signals
Conditional brake Upon presentation of a stimulus signaling that there will be no reinforcement following the conditioned stimulus “Prohibitions”, stopping current activities under certain conditions
Delayed During the pause between the conditioned signal and the delayed reinforcement "Expectation"

The transmitter located in the vesicles is released into the synaptic cleft with the help of exocytosis Its release occurs in small portions - quanta. A small number of quanta emerge from the end and are at rest. When a nerve impulse, i.e. AP reaches the presynaptic terminal, depolarization of its presynaptic membrane occurs. Its calcium channels open and calcium ions enter the synaptic plaque. The release of a large number of neurotransmitter quanta begins. Transmitter molecules diffuse through the synaptic cleft to the postsynaptic membrane and interact with its chemoreceptors. As a result of the formation of transmitter-receptor complexes, the synthesis of so-called second messengers (in particular, cAMP) begins in the subsynaptic membrane. These messengers activate ion channels on the postsynaptic membrane. Therefore, such channels are called chemodependent or receptor-gated. Those. they open upon the action of PAS on chemoreceptors. As a result of the opening of the channels, the potential of the subsynaptic membrane changes. This change is called postsynaptic potential.

In the central nervous system exciting are choline-, adren-, dopamine-, serotonergic synapses and some others. When their mediators interact with the corresponding receptors, chemodependent sodium channels open. Sodium ions enter the cell through the subsynaptic membrane. Local or spreading depolarization occurs. This depolarization is called the excitatory postsynaptic potential (EPSP).

Brake are glycine and GABAergic synapses. When a mediator binds to chemoreceptors, potassium or chloride chemodependent channels are activated. As a result, potassium ions leave the cell through the membrane.

Chlorine ions enter through it. Only arises local hyperpolarization of the subsynaptic membrane. It is called inhibitory postsynaptic potential (TPSP).

The magnitude of EPSP and IPSP is determined by the number of transmitter quanta released from the terminals, and, consequently, by the frequency of nerve impulses. Those. synaptic transmission does not obey the all-or-none law. If the amount of released excitatory transmitter is large enough, then a spreading AP can be generated in the subsynaptic membrane. IPSP, regardless of the amount of transmitter, does not spread beyond the subsynaptic membrane.

QUESTION 26. The concept of the nerve center, its functions and properties

N. center– a set of central nervous system structures, the coordinated activity of which ensures the regulation of individual body functions or a certain reflex act. The functional nerve center can be localized in different anatomical structures. For example, the respiratory center is represented by nerve cells located in the spinal cord, medulla oblongata, diencephalon, and cerebral cortex.

Depending on the function performed, there are:

sensory nerve centers;

nerve centers of autonomic functions;

motor nerve centers, etc.

Properties :

2)Irradiation of excitation. In n centers, the direction of propagation of excitation changes depending on the strength of the stimulus and the functional state of the central neurons. An increase in the strength of the stimulus leads to an expansion of the area of ​​central neurons involved in excitation - that is, irradiation of excitation.

3)Excitation summation. The process of spatial summation of afferent excitation flows from various parts of the receptive field is facilitated by the presence of hundreds and thousands of synaptic contacts on the cell membrane. The process of temporary summation in response to repeated excitation of the same receptors is caused by the summation of EPSPs on the postsynaptic membrane.

I'M CLARIFYING: The postsynaptic potential (PSP) is a temporary change in the potential of the postsynaptic membrane in response to a signal received from the presynaptic neuron. There are:

excitatory postsynaptic potential (EPSP), which provides depolarization of the postsynaptic membrane, and

inhibitory postsynaptic potential (IPSP), which provides hyperpolarization of the postsynaptic membrane.

Individual PSPs are usually small in amplitude and do not cause action potentials in the postsynaptic cell; however, unlike action potentials, they are gradual and can be summed up. There are two options for summation:

temporary - combining signals arriving via one channel (when a new pulse arrives before the previous one fades)

spatial - overlap of EPSPs of neighboring synapses

4) Presence of delay.

The duration of the reflex reaction depends on 2 factors: the speed of movement of excitation along the nerve conductors and the time of propagation of excitation through the synapse. The main time of the reflex occurs in the synaptic transmission of excitation - synaptic delay. In humans it is approximately 1 ms.

5)High fatigue. Long-term repeated stimulation of the receptive field of the reflex leads to a weakening of the reflex reaction until it disappears. This is due to the activity of synapses: the supply of the transmitter is depleted, energy resources decrease, and the postsynaptic receptor adapts to the transmitter.

6)Tone. At rest, a certain number of nerve cells are in a state of constant excitation and generate background impulse currents.

7)Plastic. The functional mobility of the nerve center can modify the pattern of reflex reactions carried out.

8)Convergence. The nerve centers of the higher parts of the brain are powerful collectors of afferent information. They contain many nerve cells that respond to various stimuli (light, sound, etc.)

9) Integration in nerve centers. To carry out complex coordinated adaptive reactions of the body, functional associations of nerve centers are formed.

10) Property of the dominant. Dominant focus is a temporarily dominant focus of increased excitability in the n center. It establishes a certain level of stationary excitation, which contributes to the summation of previously subthreshold excitations and transfer to a rhythm of work that is optimal for the given conditions. Domin. The focus suppresses neighboring foci of excitation.

11) Cephalization n. systems. The tendency to move the functions of regulation and coordination to the head parts of the central nervous system.

QUESTION 27. The phenomenon of summation of excitation in nerve centers, its types, meaning, mechanism. Properties of EPSPs and their role in the formation of summation. (Author's note: Guys, I'm sorry for this crap, but that's all I could find. I couldn't find it in the textbook)

Summation of excitation. In the work of nerve centers, a significant place is occupied by the processes of spatial and temporal summation of excitation, the main nervous substrate of which is the postsynaptic membrane. The process of spatial summation of afferent excitation flows is facilitated by the presence of hundreds and thousands of synaptic contacts on the membrane of a nerve cell. The processes of temporal summation are caused by the summation of EPSPs on the postsynaptic membrane.

In a nerve fiber, each single stimulation (if it is not of subthreshold or suprathreshold strength) causes one excitation impulse. In nerve centers, as I.M. Sechenov first showed, a single impulse in afferent fibers usually does not cause excitation, i.e. not transmitted to efferent neurons. To induce a reflex, rapid application of subthreshold stimuli one after another is necessary. This phenomenon is called temporal or consistent summation. Its essence is as follows. The quantum of transmitter released by the axon terminal when one subthreshold stimulation is applied is too small to cause an excitatory postsynaptic potential sufficient for critical depolarization of the membrane. If subthreshold impulses quickly follow one after another to the same synapse, the summation of transmitter quanta occurs, and finally its quantity becomes sufficient for the occurrence of an excitatory postsynaptic potential, and then an action potential. In addition to summation in time, in nerve centers it is possible spatial summation. It is characterized by the fact that if one afferent fiber is stimulated by a stimulus of subthreshold strength, then there will be no response, but if several afferent fibers are stimulated by a stimulus of the same subthreshold strength, then a reflex occurs, since impulses coming from several afferent fibers are summed up in the nerve center.

Excitatory postsynaptic potential. In synapses in which the postsynaptic structure is excited, there is usually an increase in permeability to sodium ions. Na+ enters the cell along a concentration gradient, which causes depolarization of the postsynaptic membrane. This depolarization is called: excitatory postsynaptic potential - EPSP. EPSP refers to local responses and, therefore, has the ability to summation. There are temporal and spatial summation.

Role in summation;

The principle of temporal summation is that impulses arrive at the presynaptic terminal with a period shorter than the EPSP period.

The essence of spatial summation is the simultaneous stimulation of the postsynaptic membrane by synapses located close to each other. In this case, the EPSPs of each synapse are summed.

If the EPSP value is large enough and reaches the critical level of depolarization (CLD), then an AP is generated. However, not all membrane regions have the same ability to generate EPSPs. Thus, the axon hillock, which is the initial segment of the axon relative to the soma, has an approximately 3 times lower threshold of electrical stimulation. Consequently, synapses located on the axonal hillock have a greater ability to generate APs than synapses on dendrites and soma. From the axonal hillock, the AP spreads into the axon and also retrogradely into the soma.

QUESTION 28. The phenomenon of transformation of the rhythm of excitations in nerve centers and its mechanisms. The role of EPSPs and ring connections in the central nervous system . (Note; The same bullshit as with the previous question - I'm sorryL)

Lat. transformatio - transformation, transformation - one of the properties of excitation in the center, which consists in the ability of a neuron to change the rhythm of incoming impulses. The transformation of the excitation rhythm is especially clearly manifested when the afferent fiber is irritated by single impulses. The neuron responds to such an impulse with a series of impulses. This is due to the occurrence of a long excitatory postsynaptic potential (the role of EPSP), against the background of which several faces (spikes-peak potentials) develop. Another reason for the occurrence of multiple pulse discharges is trace fluctuations in the membrane potential. When its value is large enough, trace oscillations can lead to the achievement of a critical level of membrane depolarization and cause the appearance of secondary spikes. In the nerve centers, a transformation of the strength of impulses can also occur: weak impulses are strengthened, and strong impulses are weakened.

QUESTION 29. Post-tetanic potentiation in nerve centers. (There is little here - but that’s all that was in the textbook)

This is an integrative phenomenon. When irritating the afferent nerve with low frequency stimuli, a reflex of a certain intensity can be obtained. If this nerve is then subjected to high-frequency rhythmic stimulation, then repeated rare rhythmic stimulation will lead to a sharp increase in the reaction.

QUESTION 30. Unilateral conduction of excitation in nerve centers. The role of synaptic structures.

Unilateral conduction of excitation. In a reflex arc that includes n centers, the excitation process spreads in one direction (from the input along the afferent pathways to the center, then along the efferent pathways to the effector).

The role of synaptic structures.

Unlike nerve and muscle fibers, which are characterized by a two-way conduction law, in a synapse excitation propagates only in one direction - from the presynaptic cell to the postsynaptic one.

31.High fatigue of nerve centers:

Fatigue- weakening of the reflex reaction until its complete disappearance, which occurs under the influence of prolonged repeated stimulation of the receptive field of the reflex. High fatigue is associated with the activity of synapses in which transmitter reserves are depleted and energy resources decrease. and high fatigue of the nerve centers occurs due to adaptation of postsynaptic receptors to transmitters.

32.tone of nerve centers and its mechanisms:

Tone-the presence of a certain background activity of the nerve center. That is, at rest, in the absence of external stimuli, a certain number of nerve cells are in a state of constant excitation, generating background impulse flows. for example, during sleep, a certain number of background active nerve cells remain in the higher parts of the brain, determining the tone of the corresponding nerve center.