Very nervous excitement. Glutamate: Boost Your Brain Glutamic Acid Neurotransmitter

Amino acid mediators are divided into two groups:

excitatory acidic(glutamate and aspartate)

inhibitory neutral(GABA, glycine, β-alanine and taurine).

GABA

GABA inhibitory mediator. It is found in the gray matter of the brain, in the Purkinje cells of the cerebellum, and in many inhibitory intermediate neurons, for example, in the striatum, spinal cord, and cortex.

GABA is formed and destroyed in the CTK GABA shunt.

Inhibition lies in the fact that it opens chloride channels, causes hyperpolarization and inhibits the excitability of the postsynaptic membrane of the effector cell.

If the inhibitory effect of GABAergic neurons is removed, then this leads to uncontrolled activity of the neural connections associated with this mediator. GABA antagonists, such as picrotoxin and bicuculline, are therefore potent convulsants.

Substances that enhance the inhibitory effect of GABA are relaxants and tranquilizers.

Various substances influence the work of GABA-reactive synapses:

Hydrazine derivatives inhibit GABA synthesis.

GABA antagonists: bicyclophosphates, norbornane.

Presynaptic blockers of GABA release: tetanotoxin.

Glycine

Glycine is the main inhibitory mediator of the spinal cord and brain stem. It opens chloride channels, causes hyperpolarization and inhibits the excitability of the postsynaptic membrane.

Glutamate

Glutamate- the main excitatory neurotransmitter of the CNS. It is present in a high concentration in the nervous tissue (10 mM) (moreover, it is higher in neurons than in glia). The direct source of glutamate in brain tissue is the reductive amination and transamination of α-ketoglutaric acid.

Five glutamate receptors have been identified.

NMDA, AMPA and kainate receptors associated with Ca 2+ channels. Under the action of glutamate, the receptors open Ca 2+ channels and launch Ca 2+ from the intercellular space into the neuroplasm.

ACPD receptors activate the inositol triphosphate system. Under the action of glutamate, they release Ca 2+ from the ER into the neuroplasm.

Activation L-AP4 receptors leads to increased hydrolysis of cGMP and blockade of incoming ion currents.

Glutamate plays an important role in synaptic plasticity and excitotoxicity, and is involved in the development of long-term potentiation, a process that underlies some forms of learning.

Enkephalins and other neuropeptides

Endorphins, dynorphins and enkephalins – neurotransmitters of a peptide nature, which are located in the spinal cord (the area responsible for conducting pain signals), in small intermediate neurons. High concentrations of enkephalins are present in the limbic system (the part that is involved in the regulation of emotions).

Among the enkephalins, Met- and Leu-enkephalin .

Three predecessors have been found : proopiomelanocortin, proenkephalin and prodynorphin.

Proopiomelanocortin contains 1 copy of ACTH, β-lipotropin, β-endorphin, Met-enkephalin. β-lipotropin , a pituitary polypeptide, is a precursor of Met-enkephalin.

Prodynorphin , a hypothalamic polypeptide, contains three copies of Leu-enkephalin and one each of β-neodynorphin and dynorphin. Dynorphin, pituitary polypeptide, is the precursor of Leu-enkephalin.

Proenkephalin contains 4 copies of Met-enkephalin, one - Leu-enkephalin.

Endorphin, dynorphin and enkephalins act on opioid receptors. These receptors are also sensitive to morphine and its derivatives. Morphine - an alkaloid isolated from the milky juice of immature poppy pods.

There are three types opiate receptors δ, μ and χ .

χ receptors bind only dynorphin, they are located mainly in the spinal cord, where they are involved in the regulation of pain signaling.

WITH δ- and μ-receptors enkephalins bind.

Opioids have both analgesic and euphoric effects. Opioids inhibit the release of substance P, a compound that appears to act as a neurotransmitter in the nerve pain pathway.

A particularly high density of receptors was found in the limbic system, the evolutionarily oldest section responsible for emotional arousal and in which the euphoric and emotional components of the analgesic effect of opiates are localized.

Glutamate in the brain is the most important neurotransmitter for excitatory synapses. Synapses that use glutamate as a transmitter are found on approximately 50% of CNS neurons. They are most common in the forebrain (telenzephalon) and the hippocampus. Receptor-controlled channels, for which glutamate serves as a ligand, are excitatory; therefore, these synapses form the most important excitatory inputs of brain systems to the cerebral cortex. They participate in learning processes. Glutamate is thus the most important CNS transmitter. Therefore, for example, the pharmacological drug ketamine, which is a glutamate antagonist, is used as an anesthetic (Table 21.2).

The release of glutamate occurs in the same way as ACh, depending on the concentration of Ca2+ ions in the presynaptic region. However, the completion of synaptic transfer occurs not through its enzymatic destruction in the synaptic cleft, but through the mechanism of transmitter reuptake by the presynaptic nerve ending. In addition, astroglia is also involved in this. Glutamate directly opens a non-specific ion channel for cations.

There are at least three main types of postsynaptic receptors, each of which has many subtypes. They differ in their ability to bind to exogenous agonists (Table 21.2). One type binds to N-methyl-D-aspartate (NMDA) and is therefore called the NMDA receptor. Some of the synapses equipped with this type of receptor have an additional mechanism in comparison with ordinary synapses. Mg2+, located in the extracellular fluid, affects them as a non-competitive blocker of the ion channel associated with this receptor (Fig. 21.9). Thus, releasing the transmitter has no effect. Another type is the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) binding receptor. If the potential of the membrane of the postsynaptic cell due to excitatory synapses that have an AMPA receptor is slightly depolarized, then the binding of Mg2+ to the NMDA receptor decreases. After that, Mg2+ releases the ion channel associated with the NMDA receptor, and sodium ions can enter the cell, causing a strong depolarization. But through the same ion channel, Ca2+ ions can also additionally enter the cell, which, through the systems of second messengers and the activation of specific proteins, contribute to long-term potentiation (long-term potentiation). This creates the basis for learning processes.

A decrease in synaptic activity (long-term depression) is possible through a similar mechanism. Since information input via the NMDA synapse is effective only when other synapses are simultaneously activated, which depolarize the cell membrane, such postsynaptic neurons can perform "logical functions". Nitric oxide NO inversely affects NMDA synapses as a retrograde messenger of the presynaptic region. It occurs additionally in the postsynaptic region if, with the help of the incoming current of Ca2+ ions, NO synthase is activated during depolarization.

Excessive excitation of many NMDA synapses can irreversibly damage postsynaptic cells (so-called excitotoxicity—cytotoxicity inherent in excitatory neurotransmitters such as glutamate and aspartate), presumably under the influence of a significant influx of Ca2+ ions. Obviously, desensitization on receptors of this type occurs very slowly. Excitotoxicity enhances many

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Many people want to improve their brain function and for this they resort to the use of nootropics. Familiarize yourself with the properties and rules for the use of glutamate.

The human body is a complex mechanism. Surely you have noticed how some people are able to think quickly, while others can “slow down”. This is influenced by a lot of factors, but there are two that can be influenced. We are now talking about the neurotransmitters GABA (slowing down) and glutamate (exciting). Although their effects on the body are opposite, glutamic acid is used to synthesize these substances.

Glutamate is now actively used in the food industry. Surely in the composition of any products you have come across the name "monosodium glutamate". This substance deceives the brain, telling it that the food is delicious.

Mechanism of glutamate

If we talk about the mechanism of the substance in a few words, then glutamate accelerates the process of information transfer between the cells of the nervous system. As a result, a person is able to act and make decisions faster. There are millions of chains of nerve cells in the brain and they are constantly exchanging information. It should be noted that each of these chains is responsible for some process.

For example, you saw something and based on this you make an appropriate decision. The first to react to the situation is the retina with the optic nerve. Then the signals are transmitted to the cerebral cortex and further along the chain to the motor organs. Glutamate can be compared to a magnet that depolarizes the cells of the nervous system. The more actively their polarity changes, the faster the signal is transmitted.

Glutamate acts on cellular structures through one of two pathways - metabotropic or ionotropic. The first is slower, but the impact lasts longer.

You probably know that neurotransmitters are synthesized by a neuron and then act on the corresponding receptors of the second one. Receptors can be compared to doors that open the way for a neurotransmitter to a second neuron. Glutamate is able to interact with the following types of receptors:

• NMDA - at rest, the receptors are "closed" with the help of a magnesium ion. As soon as a glutamate molecule enters the synaptic cleft, the “door” opens and ions depolarize. As a result, sodium enters the neuron, and potassium and calcium leave it. This process largely determines the level of human intelligence.
• AMPA - today scientists are actively working on the creation of nootropics that can actively interact with these receptors.
• Cocaine - scientists have not yet revealed all the secrets of this type of receptor. It is well established that their number is less than the two described above. However, in terms of their ability to pass potassium and sodium ions, cocaine receptors are similar to AMPA. Thus, these receptors are able to speed up the process of data transfer. But at the same time, the rate of depolarization of the postsynaptic neuron is low.

We have now considered the ionotropic pathway of the neurotransmitter. To activate metabotropic glutamate, it acts on mGlu receptors. As we said above, they have a different mechanism of work and have a longer potential.

Positive and negative properties of glutamate

Among the positive properties of the neurotransmitter, it should be noted an increase in the speed of thinking, a person remembers information faster, and also has time to do more in a short period of time. Among the negative points, it is necessary to remember the increase in impulsivity, the appearance of a feeling of anxiety, as well as excitotoxicity.

How to increase the concentration of glutamate?

Since it is synthesized from glutamic acid, it is first necessary to increase the amount of this raw material in the body. Food items include meat, fish and cheese. However, you remember that the same glutamic acid is also used for the synthesis of GABA, and what exactly needs to be synthesized at a particular point in time is decided by the body itself. So far, scientists are sure of only one natural way to increase the concentration of glutamate - stress and cramming.

The most common excitatory neurotransmitter in the brain and spinal cord is the amino acid L-glutamate. A significant example of excitatory neurons that use glutamate as a mediator are all neurons that go from the cerebral cortex to the white matter of the brain, regardless of their direction in other parts of the cerebral cortex, brainstem, or spinal cord. Glutamate is synthesized from α-ketoglutarate, which also serves as a substrate for the formation of GABA.

GABA is the most abundant inhibitory neurotransmitter in the spinal cord and brain, participating in approximately a third of all synapses in the nervous system. Millions of GABAergic neurons form the bulk of the substance of the caudate and lenticular nuclei, they are also found in large numbers in the periaqueductal gray matter, hypothalamus, and hippocampus. In addition, GABA acts as a mediator in large Purkinje cells, which are the only cells emerging from the cerebellar cortex. Axons of Purkinje cells descend to the dentate and other nuclei of the cerebellum. GABA is synthesized from glutamate by the enzyme glutamate decarboxylase.

The third amino acid neurotransmitter is glycine. Glycine is involved in the synthesis of proteins in all body tissues and is the simplest amino acid synthesized from serine during glucose catabolism. This neurotransmitter has an inhibitory effect mainly in the synapses of associative neurons in the brainstem and spinal cord.

a) Glutamate. Glutamate functions as a neurotransmitter in both ionotropic and metabotropic receptors. Ionotropic receptors include AMPA, kainate, and NMDA receptors, which got their names due to the synthetic agonists that activate them: amino-methyl-isoxazole-propionic acid, kainate, and N-methyl-D-aspartate, respectively. Kainate receptors rarely occur in isolation; most often they are combined with AMPA receptors and are part of AMPA-kainate (AMPA-K) receptors.

Ionotropic glutamate receptors. When AMPA-K receptors on the postsynaptic membrane are activated, a large amount of Na + ions immediately enter the cell and a small amount of K + ions exit the cell, which leads to the formation of an early component of the target neuron EPSP, which depolarizes the target cell membrane from -65 mV up to -50 mV. This process leads to an electrostatic expulsion of magnesium (Mg 2+) cations, which at rest close the ion channel of the NMDA receptor. Na + ions pass through the ion channel, an action potential is formed.

It is important to note that Ca 2+ ions also penetrate into the cell and, due to a long depolarization period, the duration of which reaches 500 ms from the occurrence of a single action potential, activate Ca 2+ -dependent enzymes that can change the structure of the target cell and even the number of its synaptic contacts. . The phenomenon of synaptic plasticity in response to receptor activation can be clearly observed in experimental studies on cultured sections of the rat hippocampus. This phenomenon is considered the main mechanism for the development of short-term memory. For example, the analgesic ketamine, which blocks NMDA channels, in addition to its main action, prevents the formation of memory.

A characteristic feature of repeatedly repeated activation of NMDA receptors is long-term potentiation, manifested by the occurrence of EPSP with values ​​exceeding normal values ​​even a few days later (see below - long-term depression).

The role of NMDA receptors in the development of the phenomenon of glutamate excitotoxicity has been confirmed by the development of ischemic strokes in experimental animals. It is assumed that the reason for the death of a large number of neurons was the excessive supply of Ca 2+ ions into the cell during the following events: ischemia > excessive supply of Ca 2+ ions into the cell > activation of Ca 2+ -dependent proteases and lipases > destruction of proteins and lipids > cell death . The appointment of an NMDA receptor antagonist immediately after a primary stroke can reduce the severity of ischemic brain damage.

Metabotropic glutamate receptors There are more than 100 different metabotropic glutamate receptors. All metabotropic receptors are internal membrane proteins, most of which are located on postsynaptic membranes and have an excitatory effect. Some metabotropic receptors are localized on the presynaptic membrane and are inhibitory autoreceptors.

b) GABA. GABA receptors can be either ionotropic or metabotropic.

1. Ionotropic GABA receptors. The receptors, called GABA A, are located in large numbers in the limbic lobe of the brain. Each receptor is associated with a chloride channel. Upon activation of GABA A receptors, chloride channels open, and Cl ions flow along a concentration gradient from the synaptic cleft into the cytosol. The reason for hyperpolarization, at which values ​​of -70 mV and below are achieved, is the summation of successive IPSPs.

The action of sedative-hypnotic drugs barbituric acid and benzodiazepine (for example, diazepam) is realized by activating GABA A receptors. The effect of ethanol is similar (the loss of control of social behavior under the influence of ethanol occurs due to the disinhibition of excitatory target neurons, which in the normal state are “restrained” under the influence of GABAergic influences). The mechanism of action of some volatile anesthetics also lies in the binding of receptors, due to which the ion channels remain open for a longer time.

The main antagonist occupying the active center of the receptor is the convulsant bicuculline. Another convulsant, picrotoxin, binds to protein subunits that close the ion channel in an active state.

2. Metabotropic GABA receptors. Metabotropic receptors, called GABA B, are evenly distributed in all brain structures, they are also found in peripheral autonomic nerve plexuses. Despite the fact that a large number of G-proteins of these receptors act as second messengers, a significant part of G-proteins affects a special type of postsynaptic potassium channels - GIRK channels (G-protein-coupled potassium channels of internal rectification). When the mediator is attached, the β-subunit is separated, which "pushes" K + ions through the GIRK channel, which leads to the formation of IPSP.

The response of this type of target neuron receptor is slower and weaker compared to GABA A iontophoresis, and higher frequency stimulation is required for their activation. In this regard, it is believed that GABA A receptors are not located in the outer layer of the synaptic cleft, but extrasynaptically. This assumption can be confirmed by the presence of another type of extrasynaptically located G-directed channels. These calcium channels are also voltage-dependent and are involved in providing the cell with the amount of Ca 2+ ions necessary to move synaptic vesicles across the presynaptic membrane. Upon activation of the G-Ca 2+ -ligand binding site, calcium channels are closed, which leads to a decrease in the influence of the action potential, as well as to inhibition of the original neuron (source of excitation) and other adjacent glutamatergic neurons.

In some cases, for the treatment of diseases associated with excessive reflex muscle tone (spasticity), injections of the muscle relaxant baclofen (GABA B agonist) into the subarachnoid space surrounding the spinal cord are used. Baclofen penetrates the spinal cord and inhibits the release of glutamate from sensory nerve endings, mainly by reducing the entry of large amounts of Ca 2+ ions into the cell, which occurs under the influence of excessive frequency action potentials.

3. Reuptake of glutamate and GABA. Reuptake of glutamate and GABA occurs in two ways. The left side of each figure shows that some neurotransmitter molecules are taken up from the synaptic cleft by membrane transport proteins and placed back into the synaptic vesicles. The right parts of the figures show the capture of mediator molecules by adjacent astrocytes. While in the astrocyte, glutamate is converted to glutamine by the action of glutamine synthetase. In the process of subsequent transport to the synaptic densification, glutamate is completed under the action of glutaminase and placed in the synaptic vesicle. GABA is converted to glutamate by the action of GABA transaminase. In the process of transport, glutamate is transformed into glutamine by the action of glutamine synthetase.

Returning to the area of ​​synaptic compaction, glutamine is converted under the action of glutaminase into glutamate, from which GABA is synthesized under the action of glutamate decarboxylase, the molecules of which are placed in synaptic vesicles.

Blocking of the enzyme glutamate decarboxylase is the basis of the well-known autoimmune disease - the “fettered person” syndrome.

G) Glycine. Glycine is synthesized from serine during the catabolism of glucose. The main function of this neurotransmitter is to provide negative feedback to motor neurons in the brainstem and spinal cord. When glycine is inactivated (for example, with strychnine poisoning), excruciating convulsions occur.

Reverse capture. In the area of ​​synaptic compaction, with the help of axonal carrier proteins, a rapid reuptake of glycine is carried out, followed by its placement in synaptic vesicles.

Glutamate

Physiologist Vyacheslav Dubynin on sensory transmission, NMDA receptors and the properties of glutamic acid.

At the heart of the brain is the interaction of nerve cells, and they talk to each other with the help of substances called mediators. There are quite a lot of mediators, for example, acetylcholine, norepinephrine. One of the most important mediators, and perhaps the most important, is called glutamic acid, or glutamate. If you look at the structure of our brain and what substances different nerve cells use, then glutamate is secreted by about 40% of neurons, that is, this is a very large proportion of nerve cells.

With the help of glutamate release in our brain, brain and spinal cord, the main information flows are transmitted: everything related to sensory (vision and hearing), memory, movement, until it reaches the muscles - all this is transmitted through the release of glutamic acid. Therefore, of course, this mediator deserves special attention and is being studied very actively.

In terms of its chemical structure, glutamate is a fairly simple molecule. It is an amino acid, and a food amino acid, that is, we get similar molecules simply as part of the proteins that we eat. But I must say that food glutamate (from milk, bread or meat) practically does not pass into the brain. Nerve cells synthesize this substance right at the endings of axons, right in those structures that are part of the synapses, "in place" and further isolated in order to transmit information.

Making glutamate is very easy. The starting material is α-ketoglutaric acid. This is a very common molecule, it is obtained during the oxidation of glucose, in all cells, in all mitochondria there is a lot of it. And further on this α-ketoglutaric acid, it is enough to transplant any amino group taken from any amino acid, and now we get glutamate, glutamic acid. Glutamic acid can also be synthesized from glutamine. This is also a food amino acid, glutamate and glutamine are very easily converted into each other. For example, when glutamate has completed its function in the synapse and transmitted a signal, it is further destroyed to form glutamine.

Glutamate is an excitatory neurotransmitter, that is, it is always in our nervous system, in synapses, causing nervous excitation and further signal transmission. In this, glutamate differs, for example, from acetylcholine or norepinephrine, because acetylcholine and norepinephrine can cause excitation in some synapses, inhibition in others, they have a more complex algorithm of work. And glutamate in this sense is simpler and more understandable, although you won’t find such simplicity at all, since there are about 10 types of receptors for glutamate, that is, sensitive proteins that this molecule acts on, and different receptors conduct at different speeds and with different parameters glutamate signal.

Plant evolution has found a number of toxins that act on glutamate receptors. For what it is for plants, in general, is quite clear. Plants, as a rule, are against being eaten by animals, so evolution comes up with some kind of protective toxic constructs that stop herbivores. The most powerful plant toxins are associated with algae, and it is algae toxins that can very powerfully affect the glutamate receptors in the brain and cause total excitement and convulsions. It turns out that the superactivation of glutamate synapses is a very powerful excitation of the brain, a convulsive state. Probably the most famous molecule in this series is called domoic acid, it is synthesized by unicellular algae - there are such algae, they live in the western part of the Pacific Ocean, on the coast, for example, Canada, California, Mexico. Toxin poisoning of these algae is very, very dangerous. And this poisoning sometimes happens, because zooplankton feeds on unicellular algae, all kinds of small crustaceans or, for example, bivalve mollusks, when they filter water, draw in these algal cells, and then in some mussel or oyster there is too high a concentration of domoic acid, and can be seriously poisoned.

Even human deaths have been recorded. True, they are single, but nevertheless this speaks of the power of this toxin. And very characteristic is domoic acid poisoning in the case of birds. If some seabirds, which again eat small fish that feed on zooplankton, get too much domoic acid, then a characteristic psychosis occurs: some gulls or pelicans stop being afraid of large objects and, on the contrary, attack them, that is, they become aggressive . There was a whole epidemic of such poisonings sometime in the early 1960s, and newspaper reports of this epidemic of "bird psychosis" inspired Daphne Du Maurier to write the novel The Birds, and then Alfred Hitchcock directed the classic thriller The Birds, where you see thousands of very aggressive seagulls that torment the main characters of the film. Naturally, in reality there were no such global poisonings, but nevertheless, domoic acid causes very characteristic effects, and it and molecules like it, of course, are very dangerous for the brain.

We eat glutamic acid and similar glutamate in large quantities simply with dietary proteins. Our proteins, which are found in various foods, contain 20 amino acids. Glutamate and glutamic acid are part of this twenty. Moreover, they are the most common amino acids, if you look at the structure of proteins totally. As a result, in a day with regular food, we eat from 5 to 10 grams of glutamate and glutamine. At one time, it was very difficult to believe that glutamate functions as a mediator in the brain, because it turns out that the substance that we literally consume in horse doses performs such subtle functions in the brain. There was such a logical inconsistency. But then they realized that, in fact, food glutamate practically does not pass into the brain. For this we must thank the structure called the blood-brain barrier, that is, special cells surround all the capillaries, all the small vessels that permeate the brain, and rather tightly control the movement of chemicals from the blood into the nervous system. If not for this, then some eaten cutlet or bun would cause convulsions in us, and, of course, no one needs this. Therefore, food glutamate almost does not pass into the brain and, indeed, is synthesized in order to perform mediator functions directly in synapses. However, if you eat a lot of glutamate at once, then a small amount still penetrates the brain. Then there may be a slight excitement, the effect of which is comparable to a cup of strong coffee. This effect of high doses of dietary glutamate is known and occurs quite often if a person uses glutamate in large quantities as a dietary supplement.

The fact is that our taste system is very sensitive to glutamate. Again, this is due to the fact that there is a lot of glutamate in proteins. It turns out that the evolution of the taste system, tuning in to the chemical analysis of food, singled out glutamate as a sign of protein food, that is, we must eat protein, because protein is the main building material of our body. Similarly, our taste system has learned to detect glucose very well, because glucose and similar monosaccharides are the main source of energy, and protein is the main building material. Therefore, the taste system has tuned in to identify glutamate as a signal of protein food, and along with sour, sweet, salty, bitter tastes, we have sensitive cells in the tongue that react specifically to glutamate. And glutamate is also a well-known so-called flavor additive. Calling it a flavor enhancer is not entirely correct, because glutamate has its own taste, which is as great in importance as bitter, sour, sweet and salty.

I must say that the existence of glutamate taste has been known for more than a hundred years. Japanese physiologists discovered this effect due to the fact that glutamate (in the form of soy sauce or a sauce made from seaweed) has been used in Japanese and Chinese cuisine for a very long time. Accordingly, the question arose: why are they so tasty and why does this taste so different from standard tastes? Further, glutamate receptors were discovered, and then glutamate was already used almost in its pure form (E620, E621 - monosodium glutamate), in order to be added to a variety of foods. Sometimes it happens that glutamate is blamed for all mortal sins, they call it “another white death”: salt, sugar and glutamate are white death. This, of course, is greatly exaggerated, because I repeat once again: during the day we eat from 5 to 10 grams of glutamate and glutamic acid with ordinary food. So if you add a little glutamate to your food to bring out that meaty taste, there is nothing wrong with that, although, of course, excess is not healthy.

Indeed, there are many receptors for glutamate (about 10 types of receptors), which conduct glutamate signals at different rates. And these receptors are studied primarily from the point of view of the analysis of memory mechanisms. When memory appears in our brain and in the cerebral cortex, this really means that synapses begin to work more actively between nerve cells that transmit some kind of information flow. The main mechanism for activating the work of synapses is an increase in the efficiency of glutamate receptors. Analyzing different glutamate receptors, we see that different receptors change their effectiveness in different ways. Probably the most studied are the so-called NMDA receptors. This is an abbreviation, it stands for N-methyl-D-aspartate. This receptor responds to glutamate and NMDA. The NMDA receptor is characterized by the fact that it is able to be blocked by a magnesium ion, and if a magnesium ion is attached to the receptor, then this receptor does not function. That is, you get a synapse in which there are receptors, but these receptors are turned off. If some strong, significant signal has passed through the neural network, then magnesium ions (they are also called magnesium plugs) break away from the NMDA receptor, and the synapse literally instantly starts to work many times more efficiently. At the level of information transfer, this just means recording a certain trace of memory. There is a structure in our brain called the hippocampus, there are just a lot of such synapses with NMDA receptors, and the hippocampus is perhaps the most studied structure in terms of memory mechanisms.

But NMDA receptors, the appearance and departure of the magnesium plug is the mechanism of short-term memory, because the plug can leave and then return - then we will forget something. If a long-term memory is formed, everything is much more complicated there, and other types of glutamate receptors work there, which are capable of transmitting a signal from the membrane of a nerve cell directly to nuclear DNA. And having received this signal, nuclear DNA triggers the synthesis of additional receptors in glutamic acid, and these receptors are embedded in synaptic membranes, and the synapse begins to work more efficiently. But this does not happen instantly, as in the case of knocking out a magnesium plug, but it takes several hours, requires repetition. But if this happened, then seriously and for a long time, and this is the basis of our long-term memory.

Of course, pharmacologists use glutamate receptors to influence various brain functions, mainly to reduce the excitation of the nervous system. A very famous drug is called ketamine. It works like an anesthetic. Ketamine, in addition, is known as a molecule with a narcotic effect, because hallucinations often occur when you come out of anesthesia, so ketamine is also referred to as a hallucinogenic, psychedelic drug, it is very difficult to deal with it. But in pharmacology, this often happens: a substance that is an essential drug has some side effects, which ultimately lead to the fact that the distribution and use of this substance must be very tightly controlled.

Another molecule very well known in connection with glutamate is memantine, a substance that can quite gently block NMDA receptors and, as a result, reduce the activity of the cerebral cortex in a variety of areas. Memantine is used in a fairly wide range of situations. Its pharmacy name is Akatinol. It is used to lower the overall level of arousal in order to reduce the likelihood of epileptic seizures, and perhaps the most active use of memantine is in situations of neurodegeneration and Alzheimer's disease.