What is a synapse and synaptic cleft. Regional University Synapse as a Functional Contact of Nervous Tissue

Structure of a chemical synapse

Scheme of the process of nerve signal transmission in a chemical synapse

The porocytosis hypothesis

There is significant experimental evidence that the neurotransmitter is secreted into the synaptic cleft due to the synchronous activation of the hexagonal groups of the MPV (see above) and the vesicles attached to them, which became the basis for formulating the hypothesis porocytosis(English) porocytosis). This hypothesis is based on the observation that the vesicles attached to the MPV contract synchronously upon receiving an action potential and, at the same time, secrete the same amount of the mediator into the synaptic cleft each time, releasing only a part of the contents of each of the six vesicles. The term "porocytosis" itself comes from the Greek words poro(which means pores) and cytosis(describes the transport of chemical substances across the plasma membrane of a cell).

Most of the experimental data on the functioning of monosynaptic intercellular junctions have been obtained from studies of isolated neuromuscular junctions. As in interneuronal synapses, ordered hexagonal structures are formed in the neuromuscular synapses of the MPV. Each of these hexagonal structures can be defined as a "synaptomer" - that is, a structure that is the basic unit in the process of mediator secretion. The synaptomer contains, in addition to the actual pore recesses, protein filamentous structures containing linearly ordered vesicles; the existence of similar structures has also been proven for synapses in the central nervous system (CNS).

As mentioned above, the porocytic mechanism generates a neurotransmitter quantum, but without the membrane of the individual vesicle completely merging with the presynaptic membrane. Small coefficient of variation (<3 %) у величин постсинаптических потенциалов является индикатором того, что в единичном синапсе имеются не более 200 синаптомеров , каждый из которых секретирует один квант медиатора в ответ на один потенциал действия . 200 участков высвобождения (то есть синаптомеров, которые высвобождают медиатор), найденные на небольшом мышечном волокне, позволяют рассчитать максимальный квантовый лимит, равный одной области высвобождения на микрометр длины синаптического контакта , это наблюдение исключает возможность существования квантов медиатора, обеспечивающих передачу нервного сигнала, в объеме одной везикулы.

Comparison of the porocytosis and quantum-vesicular hypotheses

Comparison of the recently accepted TBE hypothesis with the hypothesis of porocytosis can be carried out by comparing the theoretical coefficient of variation with the experimental one calculated for the amplitudes of postsynaptic electrical potentials generated in response to each individual neurotransmitter release from the presynapse. Assuming that the process of exocytosis takes place in a small synapse containing about 5,000 vesicles (50 for each micron of synapse length), postsynaptic potentials should be generated by 50 randomly selected vesicles, which gives a theoretical coefficient of variation of 14%. This value is approximately 5 times greater than the coefficient of variation of postsynaptic potentials obtained in experiments, thus, it can be argued that the process of exocytosis in the synapse is not random (does not coincide with the Poisson distribution) - which is impossible if explained in terms of the TBE hypothesis , but is consistent with the porocytosis hypothesis. The fact is that the porocytosis hypothesis assumes that all vesicles associated with the presynaptic membrane eject the mediator at the same time; at the same time, the constant amount of mediator ejected into the synaptic cleft in response to each action potential (the stability is evidenced by the low coefficient of variation of postsynaptic responses) can be quite explained by the release of a small volume of the mediator by a large number of vesicles - moreover, the more vesicles involved in the process, the the correlation coefficient becomes smaller, although this looks somewhat paradoxical from the point of view of mathematical statistics.

Classification

Chemical synapses can be classified according to their location and belonging to the corresponding structures:

  • peripheral
    • neuromuscular
    • neurosecretory (axo-vasal)
    • receptor-neuronal
  • central
    • axo-dendritic - with dendrites, including axo-spinic - with dendritic spines, outgrowths on dendrites;
    • axo-somatic - with the bodies of neurons;
    • axo-axonal - between axons;
    • dendro-dendritic - between dendrites;

Depending on the mediator, synapses are divided into

  • aminergic, containing biogenic amines (for example, serotonin, dopamine;
    • including adrenergic containing adrenaline or norepinephrine;
  • cholinergic containing acetylcholine;
  • purinergic, containing purines;
  • peptidergic containing peptides.

At the same time, only one mediator is not always produced in the synapse. Usually the main mediator is ejected along with another, which plays the role of a modulator.

By action sign:

  • exciting
  • brake.

If the former contribute to the emergence of excitation in the postsynaptic cell, then the latter, on the contrary, stop or prevent its occurrence. Usually inhibitory are glycinergic (mediator - glycine) and GABAergic synapses (mediator - gamma-aminobutyric acid).

In some synapses, postsynaptic compaction is present - an electron-dense zone consisting of proteins. According to its presence or absence, asymmetric and symmetrical synapses are distinguished. It is known that all glutamatergic synapses are asymmetric, while GABAergic synapses are symmetrical.

In cases where several synaptic extensions come into contact with the postsynaptic membrane, multiple synapses are formed.

Spiny apparatuses, in which short single or multiple protrusions of the postsynaptic membrane of the dendrite are in contact with the synaptic expansion, are special forms of synapses. Spiny apparatus significantly increase the number of synaptic contacts on the neuron and, consequently, the amount of information processed. "Non-spiky" synapses are called "sessile". For example, all GABAergic synapses are sessile.

Notes

Links

  • Saveliev A.V. Sources of variations in the dynamic properties of the nervous system at the synaptic level // Artificial intelligence. - NAS of Ukraine, Donetsk, 2006. - No. 4. - S. 323-338.

see also

5. Chemical synapses by the nature of the neurotransmitter divided into cholinergic (mediator - acetylcholine), adrenergic (norepinephrine), dopaminergic (dopamine), GABAergic (y-aminobutyric acid), etc. In the CNS, there are mainly chemical synapses, but there are also electrical excitatory synapses and electrochemical synapses.

B.Structural elements of a chemical synapse - presynaptic and postsynaptic membranes and synaptic cleft (Fig. 2.5).

At the presynaptic terminal there are synaptic vesicles (vesicles) with a diameter of about 40 nm, which are formed in the body of the neuron and are delivered to the presynaptic ending with the help of microtubules and microfilaments, where they are filled with a mediator and ATP. The mediator is formed in the nerve ending itself. The presynaptic ending contains several thousand vesicles, each of which contains from 1 to 10 thousand molecules of a chemical substance involved in the transmission of influence through the synapse and, therefore, called a mediator (intermediary). The mitochondria of the presynaptic terminal provide energy for the process of synaptic transmission. The presynaptic membrane is the part of the membrane of the presynaptic terminal that limits the synaptic cleft.

synaptic cleft has a different width (20-50 nm), contains intercellular fluid and mucopolysaccharide dense

a substance in the form of strips, bridges, which provides a connection between the pre- and postsynaptic membranes and may contain enzymes.

The postsynaptic membrane this is a thickened part of the cell membrane of the innervated cell, containing protein receptors that have ion channels and are capable of binding mediator molecules. The postsynaptic membrane of the neuromuscular junction is also called the end plate.

AT.Excitation transfer mechanism in electric synapse similar to that in a nerve fiber: AP, which occurs on the presynaptic membrane, directly electrically irritates the postsynaptic membrane and provides its excitation. Electrical synapses, as it turned out, have a certain effect on the metabolism of contacting cells. There is evidence of the presence of inhibitory electrical synapses in the CNS, but they have not been studied enough.

G.Signal transmission in chemical synapses. An action potential (AP) received at the presynaptic ending of a chemical synapse causes depolarization of its membrane, which opens voltage-dependent Ca-channels. Ca 2+ ions enter the nerve ending according to the electrochemical gradient "provide the release of the mediator into the synaptic cleft through exocytosis. Transmitter molecules entering the synaptic cleft diffuse to the postsynaptic membrane and interact with its receptors. The action of mediator molecules leads to the opening of ion channels and the movement of Na + and K + ions according to the electrochemical gradient with a predominance of the current of Na + ions into the cell, which leads to its depolarization. This depolarization is called the excitatory postsynaptic potential (EPSP), which at the neuromuscular synapse is called the end plate potential (EPP) (Fig. 2.6).

The termination of the action of the mediator released into the synaptic cleft is carried out by means of its destruction by enzymes localized in the synaptic cleft and on the postsynaptic membrane, by diffusion of the mediator into the environment, and also by reuptake by the nerve ending.

D.Characteristics of the conduction of excitation in chemical synapses.

1 . Unilateral conduction of excitation - from the presynaptic ending towards the postsynaptic membrane. This is due to the fact that the mediator is released from the presynaptic ending, and the receptors interacting with it are localized only on the postsynaptic membrane.

    Slow propagation of excitation in synapses compared with the nerve fiber is explained by the fact that it takes time to release the mediator from the presynaptic ending, the spread of the mediator in the synaptic cleft, the action of the mediator on the postsynaptic membrane. The total delay in the transmission of excitation in the neuron reaches a value of the order of 2 ms, in the neuromuscular synapse 0.5-1.0 ms.

    Low lability of chemical synapses. In the neuromuscular synapse, it is equal to 100-150 transmitted impulses per second, which is 5-6 times lower than the lability of the nerve fiber. In synapses, the central nervous system is very variable - it can be more or less. The reason for the low lability of the synapse is the synaptic delay.

4. Synaptic depression (fatigue of the synapse) -
weakening of the cell's response to afferent impulses, expressing
occurring in a decrease in postsynaptic potentials during a long
telny irritation or after it. It is explained by the cost
mediator, accumulation of metabolites, acidification of the environment
during prolonged excitation along the same lines -
crown chains.

E.electrical synapses have a gap an order of magnitude smaller than that of chemical synapses, conduct a signal in both directions without a synaptic delay, transmission is not blocked when Ca 2+ is removed, they are not very sensitive to pharmacological drugs and poisons, and are practically indefatigable, like a nerve fiber. The very low resistivity of the adjacent pre- and postsynaptic membranes ensures good electrical conductivity.

2.2. CHARACTERISTICS OF HORMONAL REGULATION

The reflex reaction may have a hormonal link, which is typical for the regulation of the functions of internal organs - vegetative functions, in contrast to somatic functions, the reflex regulation of which is carried out only by the nervous pathway (the activity of the musculoskeletal system). If the hormonal link is turned on, then this is due to the additional production of biologically active substances. For example, when exteroreceptors are exposed to strong stimuli (cold, heat, pain stimulus), a powerful stream of afferent impulses enters the central nervous system, while an additional amount of adrenaline and adrenal cortex hormones are released into the blood, playing an adaptive (protective) role.

Hormones (Greek pogtab - I excite) - biologically active substances produced by endocrine glands or specialized cells located in various organs (for example, in the pancreas, in the gastrointestinal tract). Hormones are also produced by nerve cells - neurohormones, for example, hormones of the hypothalamus (liberins and statins), which regulate the function of the pituitary gland. Biologically active substances are also produced by non-specialized cells - tissue hormones (paracrine hormones, hormones of local action, paracrine factors - parahormones). The action of hormones or parahormones directly on neighboring cells, bypassing the blood, is called paracrine action. By place of action to target organs or to other endocrine glands, hormones are divided into two groups: 1) effector hormones, acting on effector cells (for example, insulin, which regulates metabolism in the body, increases glycogen synthesis in liver cells, increases the transport of glucose and other substances through the cell membrane, increases the intensity of protein synthesis); 2) triple hormones (tropins), acting on other endocrine glands and regulating their functions (for example, ad-

pituitary renocorticotropic hormone - corticotropin (ACTH) - regulates the production of hormones by the adrenal cortex).

Types of hormone influences. Hormones have two types of influences on the organs, tissues and systems of the body: functional (play a very important role in the regulation of body functions) and morphogenetic (provide morphogenesis - growth, physical, sexual and mental development; for example, with a lack of thyroxine suffers from the development of the central nervous system, and consequently, mental development).

1. Functional influence of hormones there are three types.

Starting influence - this is the ability of the hormone to trigger the activity of the effector. For example, adrenaline triggers the breakdown of glycogen in the liver and the release of glucose into the blood, vasopressin (antidiuretic hormone - ADH) turns on the reabsorption of water from the collecting ducts of the nephron into the interstitium of the kidney.

The modulating effect of the hormone - change in the intensity of the flow of biochemical processes in organs and tissues. For example, activation of oxidative processes by thyroxin, which can take place without it; stimulation of the activity of the heart by adrenaline, which passes without adrenaline. The modulating effect of hormones is also a change in the sensitivity of tissue to the action of other hormones. For example, folliculin enhances the effect of progesterone on the uterine mucosa, thyroid hormones enhance the effects of catecholamines.

Permissive effect of hormones - the ability of one hormone to ensure the implementation of the effect of another hormone. For example, insulin is necessary for the manifestation of the action of growth hormone, follitropin is necessary for the implementation of the effect of lutropin.

2. Morphogenetic influence of hormones(for growth, physical
and sexual development) is studied in detail by other disciplines
(histology, biochemistry) and only partially - in the course of physiology (see.
ch. 6). Both types of hormone influences (morphogenetic and functional
nal) are realized through the breakdown of metabolic processes,
launched through cellular enzyme systems.

2.3. REGULATION BY METABOLITES

AND TISSUE HORMONES.

MYOGENIC MECHANISM OF REGULATION.

REGULATORY FUNCTION OF BBB

Metabolites - products formed in the body during metabolism as a result of various biochemical reactions. These are amino acids, nucleotides, coenzymes, carbonic acid, mo-

local, pyruvic, adenylic acids, ionic shift, pH changes. Regulation by metabolites in the early stages of phylogenesis was the only one. Metabolites of one cell directly affected another, neighboring cell or group of cells, which in turn acted in the same way on the following cells. (contact regulation). With the advent of hemolymph and the vascular system, metabolites began to be transmitted to other cells of the body with moving hemolymph over long distances, and this became faster. Then the nervous system appeared as a regulatory system, and even later - the endocrine glands. Metabolites, although they act mainly as local regulators, can also affect to other organs and tissues, on the activity of nerve centers. For example, the accumulation of carbonic acid in the blood leads to excitation of the respiratory center and increased respiration. An example of local humoral regulation is the hyperemia of an intensively working skeletal muscle - the accumulating metabolites provide for the expansion of blood vessels, which increases the delivery of oxygen and nutrients to the muscle. Similar regulatory effects of metabolites occur in other actively working organs and tissues of the body.

tissue hormones: biogenic amines (histamine, serotonig), prostaglandins and kinins. They occupy an intermediate position between hormones and metabolites as humoral regulatory factors. These substances exert their regulatory influence on tissue cells by changing their biophysical properties (membrane permeability, their excitability), changing the intensity of metabolic processes, the sensitivity of cell receptors, and the formation of second mediators. As a result of this, the sensitivity of cells to nervous and humoral influences changes. Therefore, tissue hormones are called modules-tori regulatory signals - they have a modulating effect. Tissue hormones are formed by non-specialized cells, but they act through specialized cell receptors, for example, two types of receptors have been found for histamine - H (and H 2. Since tissue hormones affect the permeability of cell membranes, they regulate the entry into the cell and the exit from cells of various substances and ions that determine the membrane potential, and hence the development of the action potential.

Myogenic mechanism of regulation. With the development of the muscular system in the process of evolution, the myogenic mechanism of regulation of functions gradually becomes more and more noticeable. The human body is approximately 50% muscle. This is a skeletal muscle

ra (40% of body weight), cardiac muscle, circulatory smooth muscle and lymphatic vessels, walls of the gastrointestinal tract, gall bladder, bladder and other internal organs.

The essence of the myogenic mechanism of regulation is that preliminary moderate stretching of the skeletal or cardiac muscle increases the strength of their contractions. The contractile activity of a smooth muscle also depends on the degree of filling of the hollow muscular organ, and hence its stretching. With an increase in the filling of the organ, the tone of the smooth muscle first increases, and then returns to its original level (plasticity of the smooth muscle), which ensures the regulation of vascular tone and the filling of the internal hollow organs without a significant increase in pressure in them (up to a certain value). In addition, most smooth muscles are automatic, they are constantly in some degree of contraction under the influence of impulses that arise in themselves (for example, intestinal muscles, blood vessels). The impulses that come to them through the autonomic nerves have a modulating effect - they increase or decrease the tone of smooth muscle fibers.

Regulatory function of the BBB lies in the fact that it forms a special internal environment of the brain, providing an optimal mode of activity of nerve cells. It is believed that the barrier function in this case performs special structure of the walls of the capillaries of the brain. Their endothelium has very few pores, narrow gap-left junctions between cells contain almost no windows. An integral part of the barrier are also glial cells, which form a kind of cases around the capillaries, covering about 90% of their surface. The greatest contribution to the development of ideas about the blood-brain barrier was made by L. S. Stern and her collaborators. This barrier allows water, ions, glucose, amino acids, gases to pass through, retaining many physiologically active substances: adrenaline, serotonin, dopamine, insulin, thyroxine. However, there are “windows” in it, * through which the corresponding brain cells - chemoreceptors - receive direct information about the presence of hormones and other substances in the blood that do not penetrate the barrier; brain cells secrete their neurosecrets. The areas of the brain that do not have their own blood-brain barrier are the pituitary gland, the pineal gland, some parts of the hypothalamus and the medulla oblongata.

The BBB also has a protective function - prevents the entry of microbes, foreign or toxic substances of exogenous and endogenous nature into the intercellular spaces of the brain. The BBB does not allow many medicinal substances to pass through, which must be taken into account in medical practice.

2.4. SYSTEM PRINCIPLE OF REGULATION

The maintenance of indicators of the internal environment of the body is carried out with the help of the regulation of the activity of various organs and physiological systems, combined into a single functional system - the body. The concept of functional systems was developed by P.K. Anokhin (1898-1974). In recent years, the theory of functional systems has been successfully developed by K. V. Sudakov.

BUT.The structure of a functional system. A functional system is a dynamic combination of various organs and physiological systems of the body, which is formed to achieve a useful adaptive result. For example, in order to quickly run a distance, it is necessary to maximize the activity of the cardiovascular, respiratory, nervous systems and muscles. The functional system includes the following elements: 1) control device - nerve center, representing the union of the nuclei of various levels of the central nervous system; 2) him weekend channels(nerves and hormones); 3) executive bodies - effect-ry, ensuring in the course of physiological activity the maintenance of the regulated process (indicator) at some optimal level (a useful result of the activity of the functional system); four) result receptors(sensory receptors) - sensors that receive information about the parameters of the deviation of the controlled process (indicator) from the optimal level; 5) feedback channel(input channels), informing the nerve center with the help of impulses from the receptors of the result or with the help of the direct action of chemicals on the center - information about the sufficiency or insufficiency of effector efforts to maintain the regulated process (indicator) at the optimal level ( Fig. 2.7).

Afferent impulses from the receptors of the result through the feedback channels enter the nerve center that regulates one or another indicator, the center provides a change in the intensity of the work of the corresponding organ.

When changing the intensity of the effector, the metabolic rate, which also plays an important role in the regulation of the activity of the organs of a particular functional system (the humoral process of regulation).

B.Multiparametric principle of interaction of various functional systems - the principle that determines the generalized activity of functional systems (K. V. Sudakov). The relative stability of the indicators of the internal environment of the body is the result of the coordinated activity of many

functional systems. It turned out that various indicators of the internal environment of the body are interconnected. For example, excessive intake of water into the body is accompanied by an increase in the volume of circulating blood, an increase in blood pressure, and a decrease in the osmotic pressure of the blood plasma. In a functional system that maintains the optimal level of the gas composition of the blood, the interaction of pH, P CO2 and P 02 is simultaneously carried out. A change in one of these parameters immediately leads to a change in the quantitative characteristics of other parameters. To achieve any adaptive result, an appropriate functional system is formed.

AT. Systemogenesis. According to P.K. Anokhin, systemogenesis -selective maturation and development of functional systems in ante- and postnatal ontogenesis. At present, the term "systemogenesis" is used in a broader sense, while systemogenesis is understood not only as the processes of ontogenetic maturation of functional systems, but also the formation and transformation of functional systems in the course of the life of an organism.

system-forming factors of a functional system of any level are an adaptive result useful for the life of the organism, which is necessary at the moment, and the motivation that is formed at the same time. For example, to perform a high jump with a pole, the muscles of the upper

of them limbs, in the long jump - the muscles of the lower extremities.

Heterochronism of maturation of functional systems. During antenatal ontogenesis, various structures of the body are laid down at different times and mature at different rates. Thus, the nerve center is grouped and usually matures earlier than the substrate innervated by it is laid down and matures. In ontogenesis, first of all, those functional systems mature, without which the further development of the organism is impossible. For example, of the three functional systems associated with the oral cavity, after birth, only the functional system of sucking is formed, later the functional system of chewing is formed, then the functional system of speech.

Consolidation of functional system components - integration into a functional system of individual fragments that develop in various parts of the body. Consolidation of fragments of a functional system is a critical point development of its physiological architecture. The central nervous system plays a leading role in this process. For example, the heart, blood vessels, respiratory apparatus, blood are combined into a functional system for maintaining the constancy of the gas composition of the internal environment based on the improvement of connections between various parts of the central nervous system, as well as on the basis of the development of innervation connections between the central nervous system and the corresponding peripheral structures.

All functional systems of different levels have the same architectonics(structure).

2.5. TYPES OF REGULATION OF BODY FUNCTIONS

1. Deviation regulation - a cyclic mechanism, in which any deviation from the optimal level of the regulated indicator mobilizes all the devices of the functional system to restore it at the previous level. Regulation by deviation implies the presence of a channel in the system complex negative feedback, providing a multidirectional influence: strengthening incentive management mechanisms in case of weakening process indicators or weakening incentive mechanisms in case of excessive strengthening of process indicators. For example, with an increase in blood pressure, regulatory mechanisms are activated that ensure a decrease in blood pressure, and with low blood pressure, opposite reactions are activated. Unlike negative feedback, positive

Feedback, which is rare in the body, has only a unidirectional, enhancing effect on the development of the process, which is under the control of the control complex. Therefore, positive feedback makes the system unstable, unable to ensure the stability of the regulated process within the physiological optimum. For example, if blood pressure were regulated according to the principle of positive feedback, in the case of a decrease in blood pressure, the action of regulatory mechanisms would lead to an even greater decrease, and in the case of an increase, to an even greater increase. An example of positive feedback is the increased secretion of digestive juices in the stomach after a meal, which is carried out with the help of hydrolysis products absorbed into the blood.

2. Lead control lies in the fact that the regulatory mechanisms are switched on before a real change in the parameter of the regulated process (indicator) based on information entering the nerve center of the functional system and signaling a possible change in the regulated process in the future. For example, thermoreceptors (temperature detectors) located inside the body provide temperature control of the internal regions of the body. Skin thermoreceptors mainly play the role of environmental temperature detectors. With significant deviations in the ambient temperature, prerequisites are created for a possible change in the temperature of the internal environment of the body. However, normally this does not happen, since the impulse from the thermoreceptors of the skin, continuously entering the hypothalamic thermoregulatory center, allows it to make changes in the work of the effectors of the system. until the moment of a real change in the temperature of the internal environment of the organism. Increased ventilation of the lungs during exercise begins before the increase in oxygen consumption and the accumulation of carbonic acid in human blood. This is carried out due to afferent impulses from the proprioreceptors of actively working muscles. Consequently, the impulsation of proprioceptors acts as a factor organizing the restructuring of the functioning of the functional system, which maintains the optimal level of P 02, P ss, 2 for metabolism and the pH of the internal environment ahead of time.

The advance control can be implemented using the mechanism conditioned reflex. It is shown that the conductors of freight trains in winter have a sharp increase in heat production as they move away from the departure station, where the conductor was in a warm room. On the way back, as we get closer


physical

In most synapses of the nervous system, chemicals are used to transmit signals from the presynaptic neuron to the postsynaptic neuron - mediators or neurotransmitters. Chemical signaling is carried out through chemical synapses(Fig. 14), including the membranes of pre- and postsynaptic cells and separating them synaptic cleft- area of ​​extracellular space about 20 nm wide.

Fig.14. chemical synapse

In the area of ​​the synapse, the axon usually expands, forming the so-called. presynaptic plaque or end plate. The presynaptic terminal contains synaptic vesicles- vesicles surrounded by a membrane with a diameter of about 50 nm, each of which contains 10 4 - 5x10 4 mediator molecules. The synaptic cleft is filled with mucopolysaccharide, which glues pre- and postsynaptic membranes together.

The following sequence of events has been established during transmission through a chemical synapse. When the action potential reaches the presynaptic ending, the membrane depolarizes in the synapse zone, the calcium channels of the plasma membrane are activated, and Ca 2+ ions enter the ending. An increase in intracellular calcium levels initiates exocytosis of mediator-filled vesicles. The contents of the vesicles are released into the extracellular space, and some of the mediator molecules, by diffusing, bind to the receptor molecules of the postsynaptic membrane. Among them are receptors that can directly control ion channels. The binding of mediator molecules to such receptors is a signal for the activation of ion channels. Thus, along with the voltage-dependent ion channels discussed in the previous section, there are mediator-dependent channels (otherwise called ligand-activated channels or ionotropic receptors). They open and let the corresponding ions into the cell. The movement of ions along their electrochemical gradients generates sodium depolarizing(exciting) or potassium (chlorine) hyperpolarizing (braking) current. Under the influence of a depolarizing current, a postsynaptic excitatory potential develops or end plate potential(PKP). If this potential exceeds the threshold level, voltage-gated sodium channels open and AP occurs. The rate of impulse conduction in the synapse is less than along the fiber, i.e. there is a synaptic delay, for example, in the neuromuscular synapse of a frog - 0.5 ms. The sequence of events described above is typical for the so-called. direct synaptic transmission.

In addition to receptors directly controlling ion channels, chemical transmission involves G-protein coupled receptors or metabotropic receptors.


G-proteins, so named for their ability to bind to guanine nucleotides, are trimers consisting of three subunits: α, β and g. There are a large number of varieties of each of the subunits (20 α, 6 β , 12γ). which creates the basis for a huge number of their combinations. G-proteins are divided into four main groups according to the structure and targets of their α-subunits: G s stimulates adenylate cyclase; G i inhibits adenylate cyclase; G q binds to phospholipase C; C 12 targets are not yet known. The G i family includes G t (transducin), which activates cGMP phosphodiesterase, as well as two G 0 isoforms that bind to ion channels. At the same time, each of the G proteins can interact with several effectors, and different G proteins can modulate the activity of the same ion channels. In the inactivated state, guanosine diphosphate (GDP) is bound to the α-subunit, and all three subunits are combined into a trimer. Interaction with the activated receptor allows guanosine triphosphate (GTP) to replace GDP on the α-subunit, resulting in the dissociation of α -- and βγ subunits (under physiological conditions β - and γ-subunits remain bound). Free α--and βγ-subunits bind to target proteins and modulate their activity. The free α-subunit has GTPase activity, causing hydrolysis of GTP to form GDP. As a result, α -- and βγ subunits bind again, which leads to the termination of their activity.

To date, >1000 metabotropic receptors have been identified. While channel-bound receptors cause electrical changes in the postsynaptic membrane in just a few milliseconds or less, non-channel-bound receptors take several hundred milliseconds or more to achieve an effect. This is due to the fact that a series of enzymatic reactions must take place between the initial signal and the response. Moreover, the signal itself is often "blurred" not only in time but also in space, since it has been established that the neurotransmitter can be released not from nerve endings, but from varicose thickenings (nodules) located along the axon. In this case, there are no morphologically pronounced synapses, the nodules are not adjacent to any specialized receptive areas of the postsynaptic cell. Therefore, the mediator diffuses in a significant volume of the nervous tissue, acting (like a hormone) immediately on the receptor field of many nerve cells located in various parts of the nervous system and even beyond it. This is the so-called. indirect synaptic transmission.

In the course of functioning, synapses undergo functional and morphological rearrangements. This process is named synaptic plasticity. Such changes are most pronounced during high-frequency activity, which is a natural condition for the functioning of synapses in vivo. For example, the frequency of firing of intercalary neurons in the CNS reaches 1000 Hz. Plasticity can manifest itself as either an increase (potentiation) or a decrease (depression) in the efficiency of synaptic transmission. There are short-term (seconds and minutes last) and long-term (hours, months, years) forms of synaptic plasticity. The latter are particularly interesting in that they are related to the processes of learning and memory. For example, long-term potentiation is a steady increase in synaptic transmission in response to high-frequency stimulation. This kind of plasticity can go on for days or months. Long-term potentiation is observed in all parts of the CNS, but is most fully studied at glutamatergic synapses in the hippocampus. Long-term depression also occurs in response to high-frequency stimulation and manifests itself as a long-term weakening of synaptic transmission. This type of plasticity has a similar mechanism with long-term potentiation, but develops at a low intracellular concentration of Ca2+ ions, while long-term potentiation develops at a high one.

The release of mediators from the presynaptic ending and the chemical transmission of the nerve impulse in the synapse can be influenced by mediators released from the third neuron. Such neurons and mediators can inhibit synaptic transmission or, conversely, facilitate it. In these cases, one speaks of heterosynaptic modulation - heterosynaptic inhibition or facilitation depending on the end result.

Thus, chemical transmission is more flexible than electrical transmission, since both excitatory and inhibitory actions can be carried out without difficulty. In addition, when postsynaptic channels are activated by chemical agents, a sufficiently strong current can arise that can depolarize large cells.

Mediators - application points and nature of action

One of the most difficult tasks facing neurophysiologists is the precise chemical identification of neurotransmitters acting at different synapses. To date, quite a lot of compounds are known that can act as chemical mediators in the intercellular transmission of a nerve impulse. However, only a limited number of such mediators have been accurately identified; some of which will be discussed below. In order for the mediator function of a substance in any tissue to be irrefutably proven, certain criteria must be met:

1. when applied directly to the postsynaptic membrane, the substance should cause exactly the same physiological effects in the postsynaptic cell as when the presynaptic fiber is stimulated;

2. it must be proven that this substance is released upon activation of the presynaptic neuron;

3. the action of the substance must be blocked by the same agents that suppress the natural conduction of the signal.

synapse structure

A typical synapse is an axo-dendritic chemical synapse. Such a synapse consists of two parts: presynaptic, formed by a club-shaped extension of the end of the axon of the transmitting cell and postsynaptic, represented by the contact area of ​​the cytolemma of the perceiving cell (in this case, the dendrite area). The synapse is a space separating the membranes of contacting cells, to which the nerve endings fit. The transmission of impulses is carried out chemically with the help of mediators or electrically through the passage of ions from one cell to another.

Between both parts there is a synaptic gap - a gap 10-50 nm wide between the postsynaptic and presynaptic membranes, the edges of which are reinforced with intercellular contacts.



The part of the axolemma of the club-shaped extension adjacent to the synaptic cleft is called presynaptic membrane. The section of the cytolemma of the perceiving cell that limits the synaptic cleft on the opposite side is called postsynaptic membrane, in chemical synapses it is relief and contains numerous receptors.

In the synaptic extension there are small vesicles, the so-called synaptic vesicles containing either a mediator (a mediator in the transfer of excitation), or an enzyme that destroys this mediator. On the postsynaptic, and often on the presynaptic membranes, there are receptors for one or another mediator.

Synapse classifications

Depending on the mechanism of transmission of a nerve impulse, there are

  • chemical;
  • electrical - cells are connected by highly permeable contacts using special connexons (each connexon consists of six protein subunits). The distance between cell membranes in an electrical synapse is 3.5 nm (usual intercellular is 20 nm)

Since the resistance of the extracellular fluid is small (in this case), the impulses pass without stopping through the synapse. Electrical synapses are usually excitatory.

For the nervous system of mammals, electrical synapses are less characteristic than chemical ones.

  • mixed synapses: The presynaptic action potential creates a current that depolarizes the postsynaptic membrane of a typical chemical synapse, where the pre- and postsynaptic membranes do not fit tightly together. Thus, in these synapses, chemical transmission serves as a necessary reinforcing mechanism.

The most common chemical synapses.

Chemical synapses can be classified according to their location and belonging to the corresponding structures:

  • peripheral
    • neuromuscular
    • neurosecretory (axo-vasal)
    • receptor-neuronal
  • central
    • axo-dendritic- with dendrites, incl.
      • axo-spiky- with dendritic spines, outgrowths on dendrites;
    • axo-somatic- with the bodies of neurons;
    • axo-axonal- between axons;
    • dendro-dendritic- between dendrites;

Depending on the mediator synapses are divided into

  • aminergic, containing biogenic amines (for example, serotonin, dopamine;)
    • including adrenergic containing adrenaline or norepinephrine;
  • cholinergic containing acetylcholine;
  • purinergic, containing purines;
  • peptidergic containing peptides.

At the same time, only one mediator is not always produced in the synapse. Usually the main mediator is ejected along with another, which plays the role of a modulator.

By action sign:

  • exciting
  • brake.

If the former contribute to the emergence of excitation in the postsynaptic cell (as a result of the receipt of an impulse, the membrane depolarizes in them, which can cause an action potential under certain conditions.), Then the latter, on the contrary, stop or prevent its occurrence, prevent further propagation of the impulse. Usually inhibitory are glycinergic (mediator - glycine) and GABAergic synapses (mediator - gamma-aminobutyric acid).

There are two types of inhibitory synapses: 1) a synapse, in the presynaptic endings of which a mediator is released that hyperpolarizes the postsynaptic membrane and causes the appearance of an inhibitory postsynaptic potential; 2) axo-axonal synapse, providing presynaptic inhibition. Cholinergic synapse (s. cholinergica) - a synapse in which acetylcholine is a mediator.

Some synapses have postsynaptic compaction- an electron-dense zone consisting of proteins. Synapses are distinguished by its presence or absence. asymmetrical and symmetrical. It is known that all glutamatergic synapses are asymmetric, while GABAergic synapses are symmetrical.

In cases where several synaptic extensions are in contact with the postsynaptic membrane, they form multiple synapses.

Special forms of synapses include spine devices, in which short single or multiple protrusions of the postsynaptic membrane of the dendrite are in contact with the synaptic expansion. Spiny apparatus significantly increase the number of synaptic contacts on the neuron and, consequently, the amount of information processed. "Non-spiky" synapses are called "sessile". For example, all GABAergic synapses are sessile.

The mechanism of functioning of the chemical synapse

When the presynaptic terminal is depolarized, voltage-sensitive calcium channels open, calcium ions enter the presynaptic terminal and trigger the mechanism of synaptic vesicle fusion with the membrane. As a result, the mediator enters the synaptic cleft and attaches to the receptor proteins of the postsynaptic membrane, which are divided into metabotropic and ionotropic. The former are associated with a G-protein and trigger a cascade of intracellular signal transduction reactions. The latter are associated with ion channels that open when a neurotransmitter binds to them, which leads to a change in the membrane potential. The mediator acts for a very short time, after which it is destroyed by a specific enzyme. For example, in cholinergic synapses, the enzyme that destroys the mediator in the synaptic cleft is acetylcholinesterase. At the same time, part of the mediator can move with the help of carrier proteins through the postsynaptic membrane (direct capture) and in the opposite direction through the presynaptic membrane (reverse capture). In some cases, the mediator is also absorbed by neighboring neuroglia cells.

Two release mechanisms have been discovered: with complete fusion of the vesicle with the plasmalemma and the so-called "kissed and ran away" (eng. kiss and run), when the vesicle connects to the membrane, and small molecules come out of it into the synaptic cleft, while large ones remain in the vesicle. The second mechanism, presumably, is faster than the first one, with the help of which synaptic transmission occurs at a high content of calcium ions in the synaptic plaque.

The consequence of this structure of the synapse is the unilateral conduction of the nerve impulse. There is a so-called synaptic delay is the time it takes for a nerve impulse to be transmitted. Its duration is about - 0.5 ms.

The so-called "Dale principle" (one neuron - one mediator) is recognized as erroneous. Or, as it is sometimes believed, it is refined: not one, but several mediators can be released from one cell ending, and their set is constant for a given cell.

Discovery history

  • In 1897, Sherrington formulated the concept of synapses.
  • For research on the nervous system, including synaptic transmission, in 1906 the Nobel Prize was awarded to Golgi and Ramon y Cajal.
  • In 1921, the Austrian scientist O. Loewi established the chemical nature of the transmission of excitation through synapses and the role of acetylcholine in it. Received the Nobel Prize in 1936 together with G. Dale (N. Dale).
  • In 1933, the Soviet scientist A. V. Kibyakov established the role of adrenaline in synaptic transmission.
  • 1970 - B. Katz (V. Katz, UK), U. von Euler (U. v. Euler, Sweden) and J. Axelrod (J. Axelrod, USA) received the Nobel Prize for discovering the role of norepinephrine in synaptic transmission.

1. The concept of a synapse.

2. The structure of the synapse.

3. Classification of synapses.

4. The mechanism of functioning of the chemical synapse.

5. The history of the discovery of the synapse.

Kazan (Privolzhsky) Federal University

Institute of Mechanics and Mathematics

according to age anatomy

Performed:

1st year student, group 1101

Valitova Julia.

Checked:

Rusinova S.I.

The synapse is the site of functional rather than physical contact between neurons; it transmits information from one cell to another. Synapses are usually found between the terminal branches of the axon of one neuron and dendrites ( axodendritic synapses) or body ( axosomatic synapses) of another neuron. The number of synapses is usually very large, which provides a large area for information transfer. For example, there are more than 1000 synapses on the dendrites and bodies of individual motor neurons of the spinal cord. Some brain cells can have up to 10,000 synapses (Figure 16.8).

There are two types of synapses - electrical and chemical- depending on the nature of the signals passing through them. Between the endings of the motor neuron and the surface of the muscle fiber there is neuromuscular junction, which differs in structure from interneuronal synapses, but is functionally similar to them. Structural and physiological differences between a normal synapse and a neuromuscular junction will be described later.

The structure of a chemical synapse

Chemical synapses are the most common type of synapse in vertebrates. These are bulbous thickenings of nerve endings called synaptic plaques and located in close proximity to the end of the dendrite. The cytoplasm of the synaptic plaque contains mitochondria, smooth endoplasmic reticulum, microfilaments, and numerous synaptic vesicles. Each bubble is about 50 nm in diameter and contains mediator A substance that transmits nerve signals across the synapse. The membrane of the synaptic plaque in the area of ​​the synapse itself is thickened as a result of the compaction of the cytoplasm and forms presynaptic membrane. The dendrite membrane in the area of ​​the synapse is also thickened and forms postsynaptic membrane. These membranes are separated by a gap - synaptic cleft about 20 nm wide. The presynaptic membrane is designed in such a way that synaptic vesicles can attach to it and neurotransmitters can be released into the synaptic cleft. The postsynaptic membrane contains large protein molecules that act as receptors mediators, and numerous channels and pores(usually closed), through which ions can enter the postsynaptic neuron (see Fig. 16.10, A).

Synaptic vesicles contain a neurotransmitter that is formed either in the body of the neuron (and enters the synaptic plaque, having passed through the entire axon), or directly in the synaptic plaque. In both cases, the synthesis of the mediator requires enzymes that are formed in the cell body on ribosomes. In the synaptic plaque, the neurotransmitter molecules are "packed" into vesicles, in which they are stored until they are released. The main mediators of the nervous system of vertebrates - acetylcholine and norepinephrine, but there are other mediators that will be discussed later.

Acetylcholine is an ammonium derivative whose formula is shown in fig. 16.9. This is the first known mediator; in 1920, Otto Levi isolated it from the terminals of the parasympathetic neurons of the vagus nerve in the frog heart (section 16.2). The structure of norepinephrine is discussed in detail in Sec. 16.6.6. Neurons that release acetylcholine are called cholinergic, and releasing norepinephrine - adrenergic.

Mechanisms of synaptic transmission

It is believed that the arrival of a nerve impulse in the synaptic plaque causes depolarization of the presynaptic membrane and an increase in its permeability for Ca 2+ ions. The Ca 2+ ions entering the synaptic plaque cause the fusion of synaptic vesicles with the presynaptic membrane and the release of their contents from the cell. (exocytosis), causing it to enter the synaptic cleft. This whole process is called electrosecretory conjugation. After release of the mediator, the vesicle material is used to form new vesicles filled with mediator molecules. Each vial contains about 3,000 molecules of acetylcholine.

Transmitter molecules diffuse through the synaptic cleft (this process takes about 0.5 ms) and bind to receptors located on the postsynaptic membrane that can recognize the molecular structure of acetylcholine. When a receptor molecule binds to a mediator, its configuration changes, which leads to the opening of ion channels and the entry of ions into the postsynaptic cell, causing depolarization or hyperpolarization(Fig. 16.4, A) its membranes, depending on the nature of the released mediator and the structure of the receptor molecule. The mediator molecules that caused a change in the permeability of the postsynaptic membrane are immediately removed from the synaptic cleft either by their reabsorption by the presynaptic membrane, or by diffusion from the cleft or enzymatic hydrolysis. When cholinergic synapses, acetylcholine located in the synaptic cleft is hydrolyzed by the enzyme acetylcholinesterase located on the postsynaptic membrane. As a result of hydrolysis, choline is formed, it is absorbed back into the synaptic plaque and again converted there into acetylcholine, which is stored in the vesicles (Fig. 16.10).

AT exciting In synapses, under the action of acetylcholine, specific sodium and potassium channels open, and Na + ions enter the cell, and K + ions leave it in accordance with their concentration gradients. The result is depolarization of the postsynaptic membrane. This depolarization is called excitatory postsynaptic potential(VPSP). The amplitude of the EPSP is usually small, but its duration is longer than that of the action potential. The amplitude of the EPSP changes in a stepwise manner, and this suggests that the neurotransmitter is released in portions, or "quanta", and not in the form of individual molecules. Apparently, each quantum corresponds to the release of a mediator from one synaptic vesicle. A single EPSP is usually unable to induce the threshold depolarization required for an action potential to occur. But the depolarizing effects of several EPSPs add up, and this phenomenon is called summation. Two or more EPSPs occurring simultaneously at different synapses of the same neuron can collectively induce depolarization sufficient to excite an action potential in a postsynaptic neuron. It's called spatial summation. The rapidly repeated release of the mediator from the vesicles of the same synaptic plaque under the action of an intense stimulus causes separate EPSPs that follow so often one after another in time that their effects are also summed up and cause an action potential in the postsynaptic neuron. It is called temporary summation. Thus, impulses can occur in a single postsynaptic neuron, either as a result of weak stimulation of several presynaptic neurons associated with it, or as a result of repeated stimulation of one of its presynaptic neurons. AT brake synapses, the release of the mediator increases the permeability of the postsynaptic membrane by opening specific channels for K + and Cl - ions. Moving along concentration gradients, these ions cause membrane hyperpolarization, called inhibitory postsynaptic potential(TPSP).

Mediators themselves do not have excitatory or inhibitory properties. For example, acetylcholine has an excitatory effect at most neuromuscular junctions and other synapses, but causes inhibition at the neuromuscular junctions of the heart and visceral muscles. These opposite effects are due to the events that unfold on the postsynaptic membrane. The molecular properties of the receptor determine which ions will enter the postsynaptic neuron, and these ions, in turn, determine the nature of the change in postsynaptic potentials, as described above.

electrical synapses

In many animals, including coelenterates and vertebrates, the transmission of impulses through some synapses is carried out by passing an electric current between pre- and postsynaptic neurons. The width of the gap between these neurons is only 2 nm, and the total resistance to current from the side of the membranes and the fluid filling the gap is very small. Impulses pass through the synapses without delay, and their transmission is not affected by drugs or other chemicals.

neuromuscular junction

The neuromuscular junction is a specialized type of synapse between the endings of a motor neuron (motoneuron) and endomysium muscle fibers (section 17.4.2). Each muscle fiber has a specialized area - motor end plate, where the axon of a motor neuron (motoneuron) branches, forming unmyelinated branches about 100 nm thick, passing in shallow grooves along the surface of the muscle membrane. The membrane of the muscle cell - the sarcolemma - forms many deep folds called postsynaptic folds (Fig. 16.11). The cytoplasm of motor neuron endings is similar to the contents of a synaptic plaque and releases acetylcholine during stimulation using the same mechanism as mentioned above. Changes in the configuration of receptor molecules located on the surface of the sarcolemma lead to a change in its permeability for Na + and K +, and as a result, local depolarization occurs, called end plate potential(PKP). This depolarization is quite sufficient in magnitude for the occurrence of an action potential, which propagates along the sarcolemma deep into the fiber along the system of transverse tubules ( T-system) (section 17.4.7) and causes the muscle to contract.

Functions of synapses and neuromuscular junctions

The main function of interneuronal synapses and neuromuscular junctions is to transmit a signal from receptors to effectors. In addition, the structure and organization of these sites of chemical secretion determine a number of important features of the conduction of a nerve impulse, which can be summarized as follows:

1. Unidirectional transmission. The release of the mediator from the presynaptic membrane and the localization of receptors on the postsynaptic membrane allow the transmission of nerve signals along this pathway in only one direction, which ensures the reliability of the nervous system.

2. Gain. Each nerve impulse causes enough acetylcholine to be released at the neuromuscular junction to cause a propagating response in the muscle fiber. Due to this, the nerve impulses coming to the neuromuscular junction, no matter how weak, can cause an effector response, and this increases the sensitivity of the system.

3. adaptation or accommodation. With continuous stimulation, the amount of mediator released in the synapse gradually decreases until the stores of the mediator are depleted; then they say that the synapse is tired, and further transmission of signals to them is inhibited. The adaptive value of fatigue is that it prevents damage to the effector due to overexcitation. Adaptation also takes place at the receptor level. (See description in section 16.4.2.)

4. Integration. A postsynaptic neuron can receive signals from a large number of excitatory and inhibitory presynaptic neurons (synaptic convergence); in this case, the postsynaptic neuron is able to sum up the signals from all presynaptic neurons. Due to spatial summation, the neuron integrates signals from many sources and produces a coordinated response. In some synapses, facilitation occurs, consisting in the fact that after each stimulus the synapse becomes more sensitive to the next stimulus. Therefore, successive weak stimuli can cause a response, and this phenomenon is used to increase the sensitivity of certain synapses. The facilitation cannot be considered as a temporary summation: here there is a chemical change in the postsynaptic membrane, and not an electrical summation of the postsynaptic membrane potentials.

5. Discrimination. Temporal summation at the synapse allows weak background impulses to be filtered out before they reach the brain. For example, the exteroceptors of the skin, eyes, and ears constantly receive signals from the environment that are not of particular importance to the nervous system: only changes stimulus intensities leading to an increase in the frequency of impulses, which ensures their transmission through the synapse and the proper response.

6. Braking. Signaling across synapses and neuromuscular junctions can be inhibited by certain blocking agents that act on the postsynaptic membrane (see below). Presynaptic inhibition is also possible if another axon ends at the end of the axon just above this synapse, forming here an inhibitory synapse. When such an inhibitory synapse is stimulated, the number of synaptic vesicles that are discharged in the first, excitatory synapse decreases. Such a device allows you to change the impact of a given presynaptic neuron using signals coming from another neuron.

Chemical effects on the synapse and neuromuscular junction

Chemicals perform many different functions in the nervous system. The effects of some substances are widespread and well understood (such as the excitatory effects of acetylcholine and adrenaline), while the effects of others are local and not yet clear enough. Some substances and their functions are given in Table. 16.2.

Some drugs used for mental disorders such as anxiety and depression are thought to interfere with chemical transmission at synapses. Many tranquilizers and sedatives (tricyclic antidepressant imipramine, reserpine, monoamine oxidase inhibitors, etc.) exert their therapeutic effect by interacting with mediators, their receptors or individual enzymes. For example, monoamine oxidase inhibitors inhibit the enzyme involved in the breakdown of adrenaline and norepinephrine, and most likely exert their therapeutic effect on depression by increasing the duration of these mediators. Type hallucinogens lysergic acid diethylamide and mescaline, reproduce the action of some natural mediators of the brain or suppress the action of other mediators.

A recent study on the effects of certain painkillers, opiates, heroin and morphine- showed that in the brain of mammals there are natural (endogenous) substances that cause a similar effect. All these substances that interact with opiate receptors are collectively called endorphins. To date, many such compounds have been discovered; of these, the group of relatively small peptides called enkephalins(meth-enkephalin, β-endorphin, etc.). They are believed to suppress pain, affect emotions and are related to some mental illnesses.

All of this has opened up new avenues for studying brain functions and the biochemical mechanisms underlying pain management and treatment through methods as diverse as suggestion, hypno? and acupuncture. Many other endorphin-type substances remain to be isolated, their structure and functions to be established. With their help, it will be possible to get a more complete picture of the work of the brain, and this is only a matter of time, since methods for isolating and analyzing substances present in such small quantities are constantly being improved.

RELATED ARTICLES