Synapses – Electrical & Chemical

Information is transmitted from one nerve cell to another, or from nerve cells to the effector cell, thanks to the existence of synapses, specialized intercellular junctions crucial for communication between the cells, and, therefore, between organs, organ systems, and the whole body. Moreover, synapses can be chemical and electrical (1).

In this article, we will elaborate on the principle behind the way the synapses work, their structure, and their functions.

Electrical synapse

Electrical synapses basically represent those areas of communication contact between nerve cells that are analogous to a broken link type of communication, the only communications-type link present between epithelial cells, muscle or some types of connective tissues.

This type of synaptic contact, also called nexus, in it's basic morphological as well as molecular-functional characteristics, is not different from the so-called cracked connection present in other types of tissues.

In this case, too, the degree of openness, or closeness, of the connexons, the cylindrical corridors through which ion exchanges take place, depends on the concentration of calcium ions, on the pH and cyclic adenosine monophosphate, cAMP (1).

Interestingly, this type of synaptic contact is not established only between the nerve cells but also between glial cells, as well as between nerve and glial cells, both in the central nervous system.

However, it is believed that in these cases these compounds play a predominant role in metabolic exchange rather than in alteration of the membrane charge. It should be emphasized that this role is very important in the metabolic communication between neurons and supporting cells.

Chemical Synapse

Chemical synapses differ from electrical ones based on the transmission mode. Namely, the process of transmission of information requires the existence of a mediator - a chemical mediator, a neurotransmitter, which indirectly leads to a change in charge in the area of the plasma membrane of the cell to which the information is transmitted (2).

The chemical synapse occurs between
two areas of nerve cells that establish communication - presynaptic and
postsynaptic.

By presynaptic region, from which the information is transferred, we imply the terminal part of the axon called the synaptic bud. The postsynaptic area is referred to as the portion of the plasma membrane of the nerve cell to which the information is transmitted, as well as the cytoplasm adjacent to that region of the membrane.

Between the presynaptic and postsynaptic areas, there is an intercellular space, which is called the synaptic gap due to its dimensions of about 20 nm larger than the gap between the membranes in the area of the electrical synapse.

Nerve cells also synthesize the exocytosomes at the level of the presynaptic membrane into a synaptic gap, releasing a variety of substances called neurotransmitters and neuromodulators.

These may be acetylcholine, amino acids, amino acid derivatives, or peptides. Nerve cells that synthesize peptides as neurotransmitters are precisely those cells that are referred to as neuroendocrine. Not all neurotransmitters have an activating effect, some have the opposite, inhibitory effect.

We should also emphasize that some of the neurotransmitters, such as acetylcholine and norepinephrine, not only provide communication between nerve cells but also transmit messages to the effector organs that "serve" the nerve cells of the autonomic nervous system. Acetylcholine is also a transmitter of the message to skeletal, transverse-striated muscle cells.

Chemical synapses, which are much easier to spot on preparations observed under the transmission electron microscope than the electrical ones, as they are of larger dimensions and are more morphologically complex, can be established between different nerve cell domains.

If a synapse is established between the axonal termination of one cell and the dendrites of another nerve cell, it is called an axo-dendritic synapse. If it is formed between the axons of one nerve cell and the body of another nerve cell, it is called axosomatic synapse. If the synapse is established between the dendrites of two nerve cells, it is the dendro-dendritic synapse.

If it is formed between the axons of two neurons, then it is called the axo-axonal synapse. Between the dendrites of one and the body of the other nerve cell, body-dendritic synapses are formed. Chemical synapses are often formed in the area of dendritic thorns and it is assumed that selection and control of information reception is carried out in these areas.

They can also be established "in passage", if they are formed by the free termination of one nerve cell with the lateral surface of the extension of another nerve cell.

Synapses can allow one-way information transmission but also two-way - one half of the synapse transmits information in one direction and the other in the other direction. Such synapses are called alternating synapses.

Pathway of Neurotransmitter Synthesis and Ejection

For a long time, scientists believed that, at least in the basic terms, the pathway of synthesis and ejection of neurotransmitters in a nerve cell is identical to that of the glandular cells.

According to this opinion, neurotransmitters and neuromediators would be synthesized in the nerve cell body, at the level of the polyribosome, granular endoplasmic reticulum and the Golgi apparatus. The secretory vesicles, which, being directed to the synaptic bud, are called synaptic vesicles would be separated from the Golgi region.

Axon mediates their orientation towards the presynaptic area, in which the very process of ejecting these substances into the synaptic gap would take place.

However, the fact that the
exocytosis process in the presynaptic region takes place not only at high speed
but also enormously regarding the quantity - in some neurons within one second
more than a thousand synaptic vesicles eject their contents – we today believe
that the process of their formation, at least in some cases, should not
completely equate to the classical route of synthesis and ejection into the
extracellular environment of the protein (2).

Namely, it has been shown that the membrane component of synaptic vesicles is formed in the perikaryon region in the form of probably empty vesicles of small diameter. These vesicles, called presynaptic vesicles, are detached from the trans-grid of the Golgi apparatus and reach the presynaptic region with the help of microtubules in the axon and unite with the presynaptic membrane.

Then, these regions of the membrane are separated by the endocytosis process and the thus formed endocytotic vesicles attach to the endosome present in the presynaptic region. The synaptic vesicles are separated from the endosomes by the budding process, which then enters the neurotransmitters, namely those that are non-peptide by their nature.

These neurotransmitters can be synthesized in the perikaryon but are in most cases synthesized in the cytoplasm of the axonal termination. In this way, the formed synaptic vesicles are then directed to the presynaptic membrane and, by ejecting their contents into the synaptic gap, by the exocytosis process, they begin a new endocytotic cycle that directs them towards the endosome.

This peculiar circulation of the membrane component of the synaptic vesicles in the presynaptic region is thought to provide an explanation for the abundance of these vesicles and the rate at which exocytosis takes place in the presynaptic region.

The process of recycling of the membrane component of synaptic vesicles in the presynaptic region was confirmed using exogenous peroxidase, an extracellular environment marker. If it is injected into the synaptic gap, its presence may manifest itself first within the endocytotic vesicles, then endosomes, and finally, inside the synaptic vesicles.

It should be noted, of course, that
the classical way of synthesis of a specific protein product takes place in a
nerve cell, but it is predominantly bound to secretory vesicles possessing a
dark contrasting nucleus, in other words, for neurotransmitter substances of a
peptide nature.

Synaptic Vesicles

Based on the size and morphological features, the synaptic vesicles can be classified into four categories. The first group contains vesicles with a diameter of about 50 nm and a circular shape and the contents inside are bright. These vesicles contain acetylcholine or, moreover, glutamic acid.

The second group includes synaptic vesicles, which differ from the previous ones only in shape - they are ellipsoidal in shape. Within these vesicles, there are inhibitory neurotransmitters or glycine. In the third category, synaptic vesicles with a larger diameter - over 60 nm are grouped, and a centrally located, darkly contrasted marrow is often seen inside.

These synaptic vesicles carry catecholamines. Finally, the fourth group includes those synaptic vesicles with a diameter greater than 175 nm and transmit the neuromediators of the peptide type (1).

In addition to neurotransmitters and
neuromediators, synaptic vesicles also contain ATP, ATPase, calcium ions, as
well as some enzymes that allow the processing of the neurotransmitters to be
functionally active.

The presynaptic area comprises the presynaptic membrane and a number of membrane and non-membrane components. In the cytoplasm of the presynaptic area, we can observe the mitochondria, numerous vesicles, and endosomes. In some cases, we can also observe the cisterns of the smooth endoplasmic reticulum.

Non-membrane components in the presynaptic area form an extremely precise and complex three-dimensional lattice that is associated with the presynaptic membrane and undoubtedly very significant in the controlled exocytosis process.

On preparations observed under the transmission electron microscope, dark contrasted triangular pointed projections can be observed on the cytoplasmic surface of the presynaptic membrane, directed towards the interior of the presynaptic area.

References

1. Südhof TC, Malenka RC. Understanding synapses: past, present, and future. Neuron. 2008 Nov 6;60(3):469-76. doi: 10.1016/j.neuron.2008.10.011. PMID: 18995821; PMCID: PMC3243741.  Found online at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243741/
2. Andreae LC, Burrone J. The role of spontaneous neurotransmission in synapse and circuit development. J Neurosci Res. 2018 Mar;96(3):354-359. doi: 10.1002/jnr.24154. Epub 2017 Oct 16. PMID: 29034487; PMCID: PMC5813191.  Found online at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813191/