Seizures are an important signal of the body about serious disorders. Acetylcholine - is it possible to increase intelligence

Systematic (IUPAC) name:

2-acetoxy- N,N,N-trimethylethanamine

Properties:

Chemical formula - C7H16NO + 2

Molar mass - 146.2074g mol-1

Pharmacology:

Half-life - 2 minutes

Acetylcholine (ACC) is an organic molecule that acts as a neurotransmitter in most organisms, including the human body. It is an ester of acetic acid and choline, the chemical formula of acetylcholine is CH3COO(CH2)2N+(CH3)3, the systematic (IUPAC) name is 2-acetoxy-N,N,N-trimethylethanamine. Acetylcholine is one of many neurotransmitters in the autonomic (autonomic) nervous system. It affects both the peripheral nervous system (PNS) and the central nervous system (CNS) and is the only neurotransmitter used in the motor division of the somatic nervous system. Acetylcholine is the main neurotransmitter in the autonomic ganglia. In cardiac tissue, acetylcholine neurotransmission has an inhibitory effect, which contributes to a decrease in heart rate. On the other hand, acetylcholine behaves as an excitatory neurotransmitter at the neuromuscular junctions of skeletal muscle.

History of creation

Acetylcholine (ACC) was first discovered by Henry Hallet Dale in 1915, when the effect of this neurotransmitter on cardiac tissue was observed. Otto Levi confirmed that acetylcholine is a neurotransmitter and named it Vagusstuff (vagus something) because the sample was obtained from the vagus nerve. In 1936, both received the Nobel Prize in Physiology or Medicine for their work. Acetylcholine was the first neurotransmitter discovered.

Function

Acetylcholine

Abbreviation: ACH

Sources: multiple

Orientation: multiple

Receptors: nicotinic, muscarinic

Predecessor: choline, acetyl-CoA

Synthesizing enzyme: choline acetyltransferase

Metabolizing enzyme: acetylcholinesterase

Acetylcholine, as a neurotransmitter, has effects in both the PNS (peripheral nervous system) and the CNS. Its receptors have very high binding constants. In the PNS, acetylcholine activates muscles and is the main neurotransmitter in the autonomic nervous system. In the CNS, acetylcholine, together with neurons, forms the neurotransmitter system, the cholinergic system, which promotes inhibitory activity.

In PNS

In the PNS, acetylcholine activates skeletal muscle and is the main neurotransmitter in the autonomic nervous system. Acetylcholine binds to acetylcholine receptors on skeletal muscle tissue and opens ligand-activated sodium channels in the cell membrane. Sodium ions then enter the muscle cell, begin to act in it and lead to muscle contraction. Although acetylcholine causes skeletal muscle contraction, it acts through a different type of receptor (muscarine) to suppress the contraction of heart muscle tissue.

in the autonomic nervous system

In the autonomic nervous system, acetylcholine is released:

In all postganglionic parasympathetic neurons

All preganglionic sympathicotropic neurons

The core of the adrenal gland is an altered sympathicotropic ganglion. When stimulated by acetylcholine, the adrenal medulla produces epinephrine and norepinephrine

In some postganglionic sympathicotropic tissues

In sweat gland stimulator neurons and in the sweat glands themselves

In the central nervous system

In the central nervous system, acetylcholine has some neuromodulatory properties and affects flexibility, activation, and the reward system. ACH plays an important role in improving sensory perception during waking up and also promotes alertness. Damage to cholinergic (acetylcholine-producing) systems in the brain contributes to memory impairment with. Acetylcholine is involved in. It has also recently been revealed that a decline in acetylcholine may be a major cause of depression.

Conducting paths

There are three types of acetylcholine pathways in the CNS

Through the pons to the thalamus and cerebral cortex

Through the macrocellular nucleus of the oculomotor nerve to the cortex

septohippocampal route

Structure

Acetylcholine is a polyatomic cation. Together with nearby neurons, acetylcholine forms a neurotransmitter system, the cholinergic system, in the brainstem and basal forebrain, which promotes axonal propagation to different parts of the brain. In the brainstem, this system originates from the pedunculopontal nucleus and the laterodorsal tegmental nucleus, which together make up the ventral tegmental area. In the basal forebrain, this system originates in the basal optic nucleus of Meinert and the septal nucleus:

In addition, acetylcholine acts as an important "internal" transmitter in the striatum, which is part of the nucleus basalis. It is released via the cholinergic interneuron.

Sensitivity and inhibition

Acetylcholine also has other effects on neurons - it can cause slow depolarization by blocking the tonically active K + current, which increases the sensitivity of neurons. Also, acetylcholine is able to activate cation conductors and thus directly stimulate neurons. Postsynaptic M4 muscarinic acetylcholine receptors open the internal valve of the potassium ion channel (Kir) and result in inhibition. The effect of acetylcholine on certain types of neurons may depend on the duration of cholinergic stimulation. For example, short-term irradiation of acetylcholine (several seconds) can contribute to the inhibition of cortical pyramidal neurons through muscarinic receptors associated with the G-protein subgroup alpha Gq type. Activation of the M1 receptor promotes the release of calcium from the intracellular pool, which subsequently promotes the activation of potassium conduction, which in turn inhibits the firing of pyramidal neurons. On the other hand, activation of the M1 tonic receptor is highly excitatory. Thus, the action of acetylcholine on the same type of receptor can lead to different effects in the same postsynaptic neurons, depending on the duration of receptor activation. Recent animal experiments have revealed that cortical neurons actually experience temporary and permanent changes in local acetylcholine levels when looking for a mate. In the cerebral cortex, tonic acetylcholine inhibits layer 4 of the middle spiny neurons, and in layers 2/3 and 5 excites pyramidal cells. This makes it possible to filter weak afferent impulses in layer 4 and increase the impulses that will reach layer 2/3 and layer L5 of the microcircuit exciter. As a result, this effect of acetylcholine on the layers serves to enhance the signal-to-noise ratio in the functioning of the cerebral cortex. At the same time, acetylcholine acts through nicotinic receptors and excites certain groups of inhibitory associative neurons in the cortex, which contributes to the attenuation of activity in the cortex.

Decision making process

One of the main functions of acetylcholine in the cerebral cortex is increased susceptibility to sensory stimulus, which is a form of attention. Phase increases in acetylcholine during visual, auditory and somatosensory stimulation contributed to an increase in the frequency of neuron emission in the corresponding main sensory areas of the cortex. When the cholinergic neurons in the basal forebrain are affected, the animals' ability to recognize visual cues is greatly impaired. When considering the effects of acetylcholine on thalamocortical connections, a sensory data transmission pathway, it was found that in vitro administration of the cholinergic agonist carbacholin to the auditory cortex of mice improved thalamocortical activity. In 1997 another cholinergic agonist was used and it was found that the activity was improved at the thalamoctic synapses. This discovery proved that acetylcholine plays an important role in the transmission of information from the thalamus to various parts of the cerebral cortex. Another function of acetylcholine in the cerebral cortex is the suppression of the transmission of intracortical information. In 1997, the cholinergic agonist muscarine was applied to the neocortical layers and it was found that excitatory postsynaptic potentials between intracortical synapses were suppressed. In vitro application of the cholinergic agonist carbacholin to the auditory cortex of mice also suppressed activity. Optical recording using stress-sensitive dye in the visual cortical lobes revealed a significant suppression of the state of intracortical excitation in the presence of acetylcholine. Some forms of learning and plasticity in the cerebral cortex depend on the presence of acetylcholine. In 1986, it was found that the typical synaptic redistribution in the primary visual cortex that occurs during monocular deprivation decreases with the depletion of cholinergic inputs to this area of ​​the cortex. In 1998, it was found that repeated stimulation of the basal forebrain, the main source of acetylcholine neurons, along with sound irradiation at a certain frequency, led to a redistribution of the auditory cortex for the better. In 1996, the effect of acetylcholine on experience-dependent plasticity was investigated by reducing cholinergic signals in the rat columnar cortex. In cholinergic-deficient animals, whisker mobility is significantly reduced. In 2006, it was found that activation of nicotinic and muscarinic receptors in the nucleus accumbens of the brain is required to perform tasks for which animals received food. Acetylcholine exhibited ambiguous behavior in research environments, which was identified based on the functions described above and results obtained from stimulus-based behavioral tests performed by subjects. The difference in reaction time between correctly performed tests and incorrectly performed tests in primates differed inversely between pharmacological changes in acetylcholine levels and surgical changes in acetylcholine levels. Similar data were obtained in the study, as well as in the examination of smokers after receiving a dose of nicotine (acetylcholine agonist).

Synthesis and decay

Acetylcholine is synthesized in certain neurons by the enzyme cholinetyltransferase from the constituents of choline and acetyl-CoA. Cholinergic neurons are responsible for the production of acetylcholine. An example of a central cholinergic region is the nucleus basalis of Meinert in the basal forebrain. The enzyme acetylcholinesterase converts acetylcholine to the inactive metabolites choline and acetate. This enzyme is found in excess in the synaptic cleft and its task is to quickly clear free acetylcholine from the synapse, which is extremely important for good muscle function. Certain neurotoxins are capable of inhibiting acetylcholinesterase, which leads to an excess of acetylcholine at the neuromuscular junction and causes paralysis, respiratory and cardiac arrest.

Receptors

There are two main classes of acetylcholine receptor, the nicotinic acetylcholine receptor (n-cholinergic receptor) and the muscarinic acetylcholine receptor (m-cholinergic receptor). They got their names from the ligands that activate the receptors.

N-cholinergic receptors

N-cholinergic receptors are ionotropic receptors permeable to sodium, potassium and calcium ions. Stimulated by nicotine and acetylcholine. They are divided into two main types - muscular and neural. Muscular can be partially blocked by curare, and neuron by hexonium. The main locations of the n-cholinergic receptor are muscle end plates, autonomic ganglia (sympathetic and parasympathetic) and the central nervous system.

Nicotine

Myasthenia gravis

The disease myasthenia gravis, which is characterized by muscle weakness and fatigue, develops when the body does not properly secrete antibodies against nicotinic receptors, thus inhibiting the correct transmission of the acetylcholine signal. Over time, the end plates of the motor nerve in the muscle are destroyed. For the treatment of this disease, drugs that inhibit acetylcholinesterase are used - neostigmine, physostigmine or pyridostigmine. These drugs cause endogenous acetylcholine to interact longer with its corresponding receptors before being deactivated by acetylcholinesterase in the synaptic cleft (the area between nerve and muscle).

M-cholinergic receptors

Muscarinic receptors are metabotropic and act on neurons for a longer time. Stimulated by muscarine and acetylcholine. Muscarinic receptors are located in the CNS and PNS of the heart, lungs, upper gastrointestinal tract, and sweat glands. Acetylcholine is sometimes used during cataract surgery to constrict the pupil. Atropine, contained in belladonna, has the opposite effect (anticholinergic) because it blocks m-cholinergic receptors and thereby dilates the pupil, from where the name of the plant actually comes from (“bella donna” is translated from Spanish as “beautiful woman”) - women used this plant for pupil dilation for cosmetic purposes. It is used inside the eye because corneal cholinesterase is able to metabolize topically applied acetylcholine before it reaches the eye. The same principle is used for pupil dilation, cardiopulmonary resuscitation, etc.

Substances that affect the cholinergic system

Blocking, slowing down or mimicking the action of acetylcholine is widely used in medicine. Substances that affect the acetylcholine system are either receptor agonists, stimulating the system, or antagonists, suppressing it.

There are two types of nicotinic receptors: Nm and Nn. Nm is located at the neuromuscular junction and promotes skeletal muscle contraction through end plate potential. Nn causes depolarization in the autonomic ganglion, resulting in a postganglionic impulse. Nicotinic receptors promote the release of catecholamine from the adrenal medulla and are also excitatory or inhibitory in the brain. Both Nm and Nn are connected by Na+ and k+ channels, but Nn is connected by an additional Ca+++ channel.

Acetylcholine receptor agonists/antagonists

Agonists and antagonists of the acetylcholine receptor can act on the receptors directly or indirectly by influencing the enzyme acetylcholinesterase, which leads to the destruction of the receptor ligand. Agonists increase the level of receptor activation, antagonists decrease it.

Diseases

Acetylcholine receptor agonists are used to treat myasthenia gravis and Alzheimer's disease.

Alzheimer's disease

Since the number of α4β2 acetylcholine receptors is reduced, drugs that inhibit cholinesterase, such as galantamine hydrobromide (a competitive and reversible inhibitor), are used during treatment.

Direct acting drugs The drugs described below mimic the action of acetylcholine on receptors. In small doses, they stimulate receptors, in large doses they cause numbness.

acetyl carnitine

acetylcholine

bethanechol

carbacholin

cevimeline

muscarine

• pilocarpine

  suberylcholine

  suxamethonium

Cholinesterase inhibitors

Most indirectly acting acetylcholine receptor agonists act by inhibiting the enzyme acetylcholinesterase. The resulting accumulation of acetylcholine causes prolonged stimulation of the muscles, glands, and central nervous system. These agonists are examples of enzyme inhibitors, they increase the potency of acetylcholine by slowing down its breakdown; some are used as nerve agents (sarin, VX nerve gas) or as pesticides (organophosphates and carbamates). Clinically used to reverse the action of muscle relaxants, to treat myasthenia gravis and symptoms of Alzheimer's disease (rivastigmine, which increases cholinergic activity in the brain).

Reversible active ingredients

The following substances reversibly inhibit the enzyme acetylcholinesterase (which breaks down acetylcholine), thus increasing acetylcholine levels.

Most drugs used in the treatment of Alzheimer's disease

Donepezil

Rivastigmine

• Edrophonius (distinguishes between myasthenic and cholinergic crisis)

  Neostigmine (usually used to reverse the action of neuromuscular blockers used in anesthesia, less commonly in myasthenia gravis)

  Physostigmine (used for glaucoma and anticholinergic drug overdoses)

  Pyridostigmine (for the treatment of myasthenia gravis)

  Carbamate insecticides (aldicarb)

  Huperizin A

Irreversible active substances

Inhibit the enzyme acetylcholinesterase.

echothiophate

Isofluorophate

Organophosphate insecticides (malathion, Pparathion, azinphos methyl, chlorpyrifos)

Organophosphate-containing nerve agents (sarin, VX nerve gas)

Victims of organophosphate-containing nerve agents usually die from asphyxiation because they are unable to relax the diaphragm.

Reactivation of acetylcholine esterase

Pralidoxime

acetylchoin receptor antagonists

Antimuscarinic agents

Ganglion blockers

Mecamylamine

Hexamethonium

Trimethaphan

Neuromuscular blockers

Atracurium

Cisatracurium

Doxacurium

Metocurine

Mivacurium

Pancuronium

Rocuronium

Sucinylcholine

tubocuranin

Vecuronium

Synthesis inhibitors

Organic mercury-containing substances such as methylmercury have a strong bond with sulihydryl groups, which causes dysfunction of the choline acetyltransferase enzyme. This inhibition can lead to acetylcholine deficiency, which can affect motor function.

Choline retake inhibitors

Gemicholine

Surge inhibitors

Botulinum suppresses the release of acetylcholine, and black widow venom (alpha-latrotoxin) has the opposite effect. Inhibition of acetylcholine causes paralysis. When bitten by a black widow, the content of acetylcholine drops sharply, and the muscles begin to contract. With complete exhaustion, paralysis occurs.

Other/unidentified/unknown

Surugatoxin

Chemical synthesis

Acetylcholine, 2-acetoxy-N,N,N-trimethylethyl ammonium chloride, is easily synthesized using various methods. For example, 2-chloroethanol reacts with trimethylamine and the resulting N,N,N-trimethylethyl-2-ethanolamine hydrochloride, also called choline, is acetylated with acetic acid andrigide or acetyl chloride to give acetylcholine. The second synthesis method is as follows - trimethylamine reacts with ethylene oxide, which, upon reaction with chloride hydrogen, turns into hydrochloride, which, in turn, is acetylated as already described above. Acetylcholine can also be obtained by reacting 2-chloroethanol acetate and trimethylamine.

Acetylcholine carries out the transmission of nerve impulses in cholinergic synapses. The discovery of the mediator role of acetylcholine belongs to the Austrian pharmacologist O. Levi (Loewi). Cholinergic synapses are present in both the somatic and autonomic nervous systems. Motor fibers of the somatic nervous system innervate skeletal muscles, and acetylcholine is released from their endings. The efferent pathways of the autonomic nervous system consist of two neurons: the first is located in the central nervous system (in the brainstem and spinal cord), the second is in the autonomic ganglion, which belongs to the peripheral nervous system (Fig. 5). Accordingly, the processes of the first neurons form preganglionic fibers, the second - postganglionic. In the preganglionic neurons of both the sympathetic and parasympathetic divisions of the autonomic nervous system, acetylcholine is the main mediator. The sympathetic and parasympathetic divisions differ in the mediator released in the synapses of the postganglionic fiber: in the sympathetic nervous system it is noradrenaline, in the parasympathetic nervous system it is acetylcholine.
Thus, acetylcholine serves as a transmitter of impulses from the endings of all parasympathetic postganglionic fibers, from the endings of postganglionic sympathetic fibers innervating the sweat glands, from the endings of all (both sympathetic and parasympathetic) preganglionic fibers, from the endings of the motor nerves of the striated muscles, as well as in many central synapses.

Chemically, acetylcholine is an ester of choline and acetic acid. Its synthesis takes place in the endings of nerve fibers from choline alcohol and acetyl-CoA under the influence of the enzyme choline acetyltransferase. The rate of the synthesis reaction is limited by the concentration of choline in synaptic endings. The synthesized mediator is deposited in vesicles as a result of active transport with the participation of the enzyme - Mg ^-dependent ATPase. The main mechanism for the release of acetylcholine into the synaptic cleft, resulting in the formation of a postsynaptic potential, is Ca2+-dependent exocytosis. Depolarization of the nerve ending, which increases the permeability of the presynaptic membrane for Ca2+, is a necessary condition for the release of acetylcholine.
Acetylcholine is chemically unstable, in an alkaline environment it quickly decomposes into choline and acetic acid. Its destruction in the cholinergic synapse is catalyzed by the enzyme acetylcholinesterase, discovered by O. Levy. Acetylcholinesterase is located on the postsynaptic membrane next to the cholinergic receptor and is one of the fastest acting enzymes. The rapid destruction of the mediator ensures the lability of cholinergic nerve transmission. The resulting choline is captured by the transporter proteins of the presynaptic membrane and further serves to reduce acetylcholine in the terminal (Fig. 6).

/>Fig. 6. Scheme of the structure of the cholinergic synapse (quoted from: Markova I.N., Nezhentseva M.N., 1997):
AH - acetylcholine; XP - cholinergic receptor; M - muscarinic cholinergic receptor; H - nicotinic cholinergic receptor; AChE - acetylcholinesterase; TM - transport mechanism; CA - choline acetyltransferase; (+) - activation; (-) - braking

The action of acetylcholine on the membrane consists in its reaction with cholinergic receptors that are part of the structure of the cell membrane (Fig. 7). Thus, the reaction of acetylcholine with the H-cholinergic receptor causes a change in the spatial arrangement of atoms of the protein molecule of the receptor. As a result, the size of the intermolecular pores of the membrane increases, forming a free passage for Na+ ions, and then for K+, and the cell membrane depolarizes, followed by repolarization. Changes in the receptor molecule caused by acetylcholine are easily reversible. After the transmission of the impulse, after about 1 ms, depolarization ends and normal membrane permeability is restored. By this time, the cholinergic receptor is already free from association with acetylcholine.
It is believed that the deformation of the receptor molecule caused by acetylcholine leads not only to an increase in the intermolecular pores of the membrane, but also contributes to the rejection of acetylcholine from the receptor. This rejection is necessary for the interaction of the releasing acetylcholine with acetylcholinesterase and its subsequent destruction (see Fig. 7).
Substances that affect cholinergic receptors can cause a stimulating (cholinomimetic) or depressing (cholinergic) effect.

O.
C-0-CH2CH2-N(CH3)3


/ C-0-CH2CH2-N(CH3)3
ch3
Rice. 7. Scheme of the interaction of acetylcholine with the cholinergic receptor
and acetylcholinesterase (quoted from: Zakusov V.V., 1973):
XP - cholinergic receptor; AChE - acetylcholinesterase; A - anode center of XP and AChE; E - AChE esterase center and ChR esterophilic center
Pharmacological substances can affect the following stages of synaptic transmission of cholinergic synapses: the synthesis of acetylcholine; 2) mediator release process; 3) interaction of acetylcholine with cholinergic receptors; 4) destruction of acetylcholine; 5) capture by the presynaptic ending of choline, which is formed during the destruction of acetylcholine. For example, at the level of presynaptic endings, botulinum toxin acts, which prevents the release of the neurotransmitter. Transport of choline across the presynaptic membrane (neuronal uptake) is inhibited by hemicholine. Cholinomimetics (pilocarpine, cytisine) and anticholinergics (M-cholinergic blockers, ganglionic blockers and peripheral muscle relaxants) have a direct effect on cholinergic receptors. To inhibit the enzyme acetylcholinesterase, anticholinesterase agents (prozerin) can be used.

Acetylcholine- one of the most important neurotransmitters, it carries out neuromuscular transmission, is the main one in the parasympathetic nervous system. Destroyed by an enzyme acetylcholinesterase.

It is used as a medicinal substance and in pharmacological research.

Medicine

Peripheral muscarine-like action (muscarine is the one in fly agaric):

- slow heart rate

- spasm of accommodation

downgrade blood pressure

- expansion of peripheral blood vessels

- contraction of the muscles of the bronchi, gall and bladder, uterus

- increased peristalsis of the stomach, intestines,

- increased secretion of digestive, sweat, bronchial, lacrimal glands, miosis.

Pupil constriction is associated with a decrease in intraocular pressure.

Acetylcholine plays an important role as a mediator of the central nervous system (transmission of impulses in the brain, small concentrations facilitate, and large ones inhibit synaptic transmission).

Changes in the metabolism of acetylcholine can lead to impaired brain function. The deficiency largely determines the picture of the disease - Alzheimer's disease.

Some centrally acting antagonists are psychotropic drugs. An overdose of antagonists can have a hallucinogenic effect.

Why do you need

Formed in the body takes part in the transmission of nervous excitation in the central nervous system, vegetative nodes, endings of parasympathetic, motor nerves.

Acetylcholine associated with memory functions. A decrease in Alzheimer's disease leads to a weakening of memory.

Acetylcholine plays an important role in waking up and falling asleep. Awakening occurs when the activity of cholinergic neurons increases.

Physiological properties

In small doses, it is a physiological transmitter of nervous excitation, and in large doses it can block the transmission of excitation.

This neurotransmitter is affected by smoking and eating fly agarics.

Acetylcholine is not the most famous substance, but it plays an important role in processes such as memory and learning. Let's lift the veil of secrecy over one of the most underestimated neurotransmitters in our nervous system.

First among equals

Figure 1. Otto Loewy's classic experiment in identifying the chemical mediators of nerve impulse transmission (1921). Objects - isolated and immersed in saline solution hearts of two frogs (donor and recipient). The description is given in the text. Figure from en.wikipedia.org, adapted.

In the popular scientific literature of a medical and neurophysiological orientation, most often it comes to three neurotransmitters: dopamine, serotonin and norepinephrine. This is largely due to the fact that normal and disease states associated with changes in the level of these neurotransmitters are more accessible to understanding and arouse more interest among readers. I have already written about these substances, now it is time to pay attention to one more mediator.

It will be about acetylcholine, and it will be symbolic, given that he was first open neurotransmitter. At the beginning of the 20th century, there was a dispute between scientists about how a signal is transmitted from one nerve cell to another. Some believed that an electric charge, having run through one nerve fiber, is transmitted to another through some thinner "wires". Their opponents argued that there are substances that carry a signal from one nerve cell to another. Basically, both sides were right: there are chemical and electrical synapses. However, supporters of the second hypothesis turned out to be "to the right" - chemical synapses predominate in the human body.

To understand the peculiarities of signal transmission from one cell to another, the physiologist Otto Loewy conducted simple but elegant experiments (Fig. 1). He stimulated the frog's vagus nerve with an electric current, which led to a decrease in the heart rate *. Then Loewy collected the liquid around this heart and applied it to the heart of another frog - and it also slowed down. This proved the existence of a certain substance that transmits a signal from one nerve cell to another. Loewy named the mysterious substance vagusstoff("substance of the vagus nerve"). Now we know it under the name acetylcholine. The issue of chemical synaptic transmission was also dealt with by the Briton Henry Dale, who discovered acetylcholine even earlier than Loewy. In 1936, both scientists received the Nobel Prize in Physiology or Medicine "for their discoveries related to the chemical transmission of nerve impulses."

* - About how our heart contracts - about automatism, conducting pacemakers and even funny channels - read in the review " » . - Ed.

Acetylcholine (Fig. 2) is produced in nerve cells from choline and acetylcoenzyme-A (acetyl-CoA). The enzyme acetylcholinesterase, located in the synaptic cleft, is responsible for the destruction of acetylcholine; this enzyme will be discussed in detail later. The structural plan of the acetylcholinergic system of the brain is similar to the structure of other neurotransmitter systems (Fig. 3). There are a number of structures in the brainstem that secrete acetylcholine, which travels along the axons to the basal ganglia of the brain. It has its own acetylcholine neurons, whose processes diverge widely in the cortex and penetrate into the hippocampus.

Figure 3. Acetylcholine system of the brain. We see that in the deep parts of the brain there are clusters of nerve cells (in the forebrain and brainstem), which send their processes to various parts of the cortex and subcortical regions. At the end points, acetylcholine is released from neuronal endings. The local effects of a neurotransmitter differ depending on the type of receptor and its location. MS - medial septal nucleus, DB - Broca's diagonal ligament, nBM - basal magnocellular nucleus (Meitner's nucleus); PPT - pedunculopontine tegmental nucleus, LDT - lateral dorsal tegmental nucleus (both nuclei are in the reticular formation of the brainstem). Drawing from , adapted.

Acetylcholine receptors are divided into two groups - muscarinic And nicotine. Stimulation of muscarinic receptors leads to a change in the metabolism in the cell through the system of G-proteins* ( metabotropic receptors), and the effect on nicotine - to a change in the membrane potential ( ionotropic receptors). This is due to the fact that nicotinic receptors are associated with sodium channels on the surface of cells. The expression of receptors differs in different parts of the nervous system (Fig. 4).

* - About the spatial structures of several representatives of the huge family of GPCR receptors - membrane receptors that act through the activation of the G-protein - are available in the articles: " Receptors in active form"(about the active form of rhodopsin)," Structures of GPCR receptors "in the piggy bank""(about dopamine and chemokine receptors)," Mood transmitter receptor(about two serotonin receptors). - Ed.

Figure 4. Distribution of muscarinic and nicotinic receptors in the human brain. Drawing from the site, adapted.

Mediator of memory and learning

The acetylcholine system of the brain is directly related to such a phenomenon as synaptic plasticity- the ability of a synapse to increase or decrease the release of a neurotransmitter in response to an increase or decrease in its activity. Synaptic plasticity is an important process for memory and learning, so scientists sought to find it in the part of the brain responsible for these functions - in the hippocampus. A large number of acetylcholine neurons direct their processes to the hippocampus, and there they influence the release of neurotransmitters from other nerve cells. The way this process is carried out is quite simple: various nicotinic receptors (mainly α 7 and β 2 types) are located on the body of the neuron and its presynaptic part. Their activation will lead to the fact that the passage of the signal through the innervated cell will be simplified, and it is more likely to pass to the next neuron. The greatest influence of this kind is experienced by GABAergic neurons - nerve cells whose neurotransmitter is γ-aminobutyric acid.

GABAergic neurons are an important part of the system that generates the electrical rhythms of our brain. These rhythms can be recorded and studied using an electroencephalogram, a widely available research method in neurophysiology. Rhythms of different frequencies are indicated by Greek letters: 8–14 Hz - alpha rhythm, 14–30 Hz - beta rhythm, and so on. The use of acetylcholine receptor stimulants causes theta (0.4–14 Hz) and gamma (30–80 Hz) rhythms to occur in the brain. These rhythms, as a rule, accompany active cognitive activity. Stimulation of postsynaptic muscarinic acetylcholine receptors located on the neurons of the hippocampus (memory center) and prefrontal cortex (center of complex behaviors) leads to the excitation of these cells and the generation of the rhythms mentioned above. They accompany various cognitive activities - for example, building a temporal sequence of events.

The hippocampus and prefrontal cortex play an important role in learning. From the point of view of reflexes, any learning occurs in two ways. Let's say you are an experimenter and the object of your experiment is a mouse. In the first case, a light is turned on in its cage (the conditioned stimulus), and the rodent receives a piece of cheese (the unconditioned stimulus) before the light goes out. The emerging reflex can be called detainees. In the second case, the light also turns on, but the mouse receives a treat some time after the light is turned off. This type of reflex is called trace. Reflexes of the second type depend on the awareness of stimuli more than reflexes of the first type. Inhibition of the activity of the acetylcholinergic system leads to the fact that trace reflexes are not developed in animals, although there are no problems with delayed ones.

When comparing the secretion of acetylcholine in the brains of rats that developed both types of reflexes, interesting data were obtained. Rats that successfully mastered the temporal relationship between the conditioned and unconditioned stimulus showed a significant increase in acetylcholine levels in the medial prefrontal cortex (Fig. 5) compared to the hippocampus. Especially significant was the difference in the levels of acetylcholine in rats that developed a trace reflex. Those rodents that did not cope with both tasks found approximately equal levels of the neurotransmitter in the studied brain regions (Fig. 6). Based on this, it can be concluded that the prefrontal cortex plays a greater role directly in learning, and the hippocampus stores the acquired knowledge.

Figure 5 Acetylcholine release in the hippocampus (HPC) and prefrontal cortex (PFC) of rats upon successful reflex training. The maximum level of acetylcholine is observed in the prefrontal cortex during the development of the trace reflex. Drawing from .

Figure 6. Acetylcholine release in the hippocampus (HPC) and prefrontal cortex (PFC) of rats in the event of a “failure” in learning. Almost the same content of acetylcholine is recorded in the two zones, regardless of the reflex. Drawing from.

Attention receptors

Figure 7. Variety of acetylcholine receptors (nAChRs) in the layers of the prefrontal cortex. Drawing from .

For learning, not only intelligence or memory capacity is important, but also attention. Without attention, even the most successful student will be a loser. Acetylcholine is also involved in the processes that regulate attention.

Attention - focused perception or thinking about a problem - is accompanied by increased activity in the prefrontal cortex. Acetylcholine fibers are sent to the frontal cortex from the deep parts of the brain. Due to the fact that we often need a quick switching of attention, it is quite logical that nicotinic (ionotropic) acetylcholine receptors, and not muscarinic ones, which cause slower and predominantly structural changes in neurons, are involved in the regulation of attention. Damage to acetylcholine structures in the deep brain reduces the activity of the medial prefrontal cortex and impairs attention. In addition, the interaction of deep acetylcholine structures with the prefrontal cortex is not limited to upstream signals. The neurons of the frontal cortex also send their signals to the underlying regions, which allows you to create a self-regulating attention maintenance system. Attention is maintained by the action of acetylcholine on presynaptic and postsynaptic receptors (Fig. 7).

When talking about nicotinic receptors and attention, the question arises of improving cognitive functions through smoking, that is, introducing an additional dose of nicotine, albeit in the form of cigarette smoke. The situation here is pretty clear, and the results do not give smokers an extra argument in favor of their addiction. Nicotine, which comes from outside, disrupts the normal development of the brain, which can lead to attention disorders(for many years). If we compare smokers and non-smokers, then the first indicators of attention are worse than those of their opponents. Improved attention in smokers occurs when they smoke a cigarette after a long abstinence, when their bad mood and cognitive problems disappear with the smoke.

Medicine for memory

If normally the acetylcholinergic system of our brain is responsible for memory, attention and learning, then diseases in which this type of transmission in our brain is disturbed should manifest themselves with the corresponding symptoms: loss of memory, decreased attention and ability to learn new things. Here we must immediately make a reservation that in the course of normal aging, the vast majority of people have a reduced ability to memorize new things, and mental alertness in general. If these disturbances are severe enough to interfere with an older person's activities and daily needs (self-care), then doctors may suspect dementia. If you want to learn more about dementia, I recommend starting with WHO newsletter dedicated to this pathology.

Strictly speaking, dementia is not a single disease, but a syndrome occurring in a number of diseases. One of the most common diseases that leads to dementia is Alzheimer's disease. It is believed that in Alzheimer's disease, the pathological protein β-amyloid accumulates in nerve cells, which disrupts the activity of nerve cells, which ultimately leads to their death. In addition to this theory, there are a number of others that have their own evidence. It is likely that in Alzheimer's disease different processes occur in the brain cells of different patients, but they lead to similar symptoms. However, β-amyloid is interesting in that it can suppress the effect that acetylcholine has on the cell via nicotinic receptors. If we succeed in intensifying acetylcholinergic transmission, then we can reduce the manifestations of the disease and prolong independent life for a person with dementia.

Drugs used in dementia include inhibitors of acetylcholinesterase (AChE), an enzyme that breaks down acetylcholine in the synaptic cleft. The use of AChE inhibitors leads to an increase in the content of acetylcholine in the interneuronal space and an improvement in signal transmission. A study on the effectiveness of AChE inhibitors in Alzheimer's disease has determined that they are able to reduce the symptoms of the disease and slow its progression. The three most commonly used drugs from this group are rivastigmine, galantamine and donepezil- are comparable in terms of efficiency and safety. There is also a small but successful experience with AChE inhibitors in the treatment of musical hallucinations in the elderly.

With the help of acetylcholine, our brain learns, focuses attention on various objects and phenomena of the surrounding world. Our memory "works" on acetylcholine, and its deficiency can be compensated with the help of drugs. I hope you enjoyed your introduction to acetylcholine.

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We know very little about the brain and intellectual abilities. However, it is safe to say that one neurotransmitter, acetylcholine, is able to increase human cognitive abilities. According to Darwin's theory, this neurotransmitter should be synthesized more actively with each new generation. Of course, this statement is true if a person does not degrade.

However, today we will not talk about evolution, but we will talk about this mediator in more detail, not forgetting to mention ways to increase its concentration. It should be said that increasing the level of acetylcholine will not make you happy, but it can speed up the process of assimilation of new information. Simply put, you will learn better.

Acetylcholine: what is it?

The neurotransmitter is responsible not only for the intellectual abilities of a person, but also for neuro-muscular connections, including autonomic ones. Note that this is one of the first substances of this group, which was discovered by scientists, and this happened at the beginning of the last century. It is important to remember that high doses of acetylcholine lead to a slowdown in the body, and small ones contribute to its acceleration. The process of neurotransmitter synthesis is activated during the receipt of new information or the reproduction of the old one.

The substance is produced by the nerve terminals of the axons, which are the junction of two neurons. The synthesis of acetylcholine requires two substances:

Acetyl coenzyme (CoA) is made from glucose.

Choline - found in some foods.

After that, the neurotransmitter is placed in a kind of round-shaped containers called vesicles and sent to the presynaptic ending of the neuron. After the vesicle fuses with the cell membrane, acetylcholine is released into the synaptic cleft.

Acetylcholine can be retained in the synaptic cleft, penetrate into the next neuron, or be returned back. In the latter case, the neurotransmitter is placed back into the vesicles. Any neurotransmitter tends to connect with its receptors located on the second neuron. Figuratively speaking, the receptor is the door, and the neurotransmitter is the key to it.

In this case, there are two types of keys, each of which is able to open a certain type of "door" - muscarinic and nicotine. For a complete description of the process, it is necessary to add that a special enzyme, acetylcholinesterase, monitors the balance of the substance in the synaptic cleft. If you use nootropics in large quantities, then after increasing the concentration of acetylcholine to a certain level, this enzyme will start working and destroy the excess of the neurotransmitter into its constituent elements.

Alzheimer's disease dramatically impairs memory, which is precisely due to the excessive activity of acetylenesterase. Now, in the treatment of this disease, drugs that can inhibit the enzyme show quite good results. However, acetylenesterase inhibitors have one drawback - a high concentration of acetylcholine can harm the body.

Moreover, the side effects can be quite serious, up to death. Some nerve gases can be classified as acetylenesterase inhibitors. Under their influence, the concentration of the neurotransmitter exceeds the permissible limits, which leads to muscle contraction.

Positive effects of acetylcholine and its disadvantages

Let's start with the positive effects that the neurotransmitter we are considering today has:

The cognitive ability of the brain increases and the person becomes smarter.

Improves memory.

The work of neuro-muscular connections improves - this is extremely useful in sports. Since the body quickly adapts to stress.

No narcotic substances can increase the level of the neurotransmitter, but will lead to the exact opposite effect - the production of acetylcholine is maximally suppressed by hallucinogens.

It helps to make smart plans, and you will make fewer stupid mistakes due to impulsive decisions.

There are only two disadvantages of this neurotransmitter:

Harmful in a stressful situation, as it slows down the ability to make quick decisions.

At high concentrations, it slows down the work of the whole organism.

However, here it is necessary to make a small correction - all people are individual, if you have a combination of high concentrations of acetylcholine and glutamate, then you will be faster and more determined. At the same time, the intellectual potential will not undergo serious changes.

We also note that the neurotransmitter begins to be more actively produced not only when new information arrives, but also due to brain and body training.

To increase the concentration of the neurotransmitter, the following supplements can be used: acetyl l-carnitine, DMAE, lecithin, hyperzine, Alzheimer's medications, hyperzine. Scopolamine, atropine and diphenhydramine will help reduce the level of the substance. We also recommend eating right so that the concentration of acetylcholine is high and, first of all, pay attention to eggs with nuts.

If you play sports, then acetylcholine will help you achieve better results.