![Chemical synapse schema cropped](https://upload.wikimedia.org/wikipedia/commons/3/30/Chemical_synapse_schema_cropped.jpg)
Chemical synapses are biological junctions through which
neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
s' signals can be sent to each other and to non-neuronal cells such as those in
muscle
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
s or
gland
In animals, a gland is a group of cells in an animal's body that synthesizes substances (such as hormones) for release into the bloodstream (endocrine gland) or into cavities inside the body or its outer surface (exocrine gland).
Structure
De ...
s. Chemical synapses allow neurons to form
circuits within the
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
. They are crucial to the
biological computations that underlie
perception
Perception () is the organization, identification, and interpretation of sensory information in order to represent and understand the presented information or environment. All perception involves signals that go through the nervous system ...
and
thought
In their most common sense, the terms thought and thinking refer to conscious cognitive processes that can happen independently of sensory stimulation. Their most paradigmatic forms are judging, reasoning, concept formation, problem solving, a ...
. They allow the
nervous system
In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes th ...
to connect to and control other systems of the body.
At a chemical synapse, one neuron releases
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neuro ...
molecules
A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioche ...
into a small space (the
synaptic cleft
Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous syste ...
) that is adjacent to another neuron. The neurotransmitters are contained within small sacs called
synaptic vesicle
In a neuron, synaptic vesicles (or neurotransmitter vesicles) store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulse ...
s, and are released into the synaptic cleft by
exocytosis
Exocytosis () is a form of active transport and bulk transport in which a cell transports molecules (e.g., neurotransmitters and proteins) out of the cell ('' exo-'' + ''cytosis''). As an active transport mechanism, exocytosis requires the use o ...
. These molecules then bind to
neurotransmitter receptor
A neurotransmitter receptor (also known as a neuroreceptor) is a membrane receptor protein that is activated by a neurotransmitter. Chemicals on the outside of the cell, such as a neurotransmitter, can bump into the cell's membrane, in which the ...
s on the postsynaptic cell. Finally, the neurotransmitters are cleared from the synapse through one of several
potential mechanisms including enzymatic degradation or re-uptake by
specific transporters either on the
presynaptic cell
Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in neuromuscular junction, muscles or glands. Chemical synapses allow neurons to form biological neural ...
or on some other
neuroglia
Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form mye ...
to terminate the action of the neurotransmitter.
The
adult
An adult is a human or other animal that has reached full growth. In human context, the term ''adult'' has meanings associated with social and legal concepts. In contrast to a " minor", a legal adult is a person who has attained the age of major ...
human
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
is estimated to contain from 10
14 to 5 × 10
14 (100–500 trillion) synapses. Every cubic millimeter of
cerebral cortex
The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting of ...
contains roughly a billion (
short scale
The long and short scales are two of several naming systems for integer power of 10, powers of ten which use some of the same terms for different magnitudes.
For whole numbers smaller than 1,000,000,000 (109), such as one thousand or one m ...
, i.e. 10
9) of them. The number of synapses in the human
cerebral cortex
The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting of ...
has separately been estimated at 0.15 quadrillion (150 trillion)
The word "synapse" was introduced by Sir
Charles Scott Sherrington
Sir Charles Scott Sherrington (27 November 1857 – 4 March 1952) was an eminent English neurophysiologist. His experimental research established many aspects of contemporary neuroscience, including the concept of the spinal reflex as a system ...
in 1897.
Chemical synapses are not the only type of biological synapse:
electrical
Electricity is the set of physical phenomena associated with the presence and motion of matter that has a property of electric charge. Electricity is related to magnetism, both being part of the phenomenon of electromagnetism, as described by ...
and
immunological synapse
In immunology, an immunological synapse (or immune synapse) is the interface between an antigen-presenting cell or target cell and a lymphocyte such as a T/B cell or Natural Killer cell. The interface was originally named after the neuronal syn ...
s also exist. Without a qualifier, however, "synapse" commonly refers to chemical synapse.
Structure
Synapses are functional connections between neurons, or between neurons and other types of cells. A typical neuron gives rise to several thousand synapses, although there are some types that make far fewer. Most synapses connect
axon
An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action po ...
s to
dendrite
Dendrites (from Greek δένδρον ''déndron'', "tree"), also dendrons, are branched protoplasmic extensions of a nerve cell that propagate the electrochemical stimulation received from other neural cells to the cell body, or soma, of the n ...
s,
but there are also other types of connections, including axon-to-cell-body,
axon-to-axon,
[
][
Axons terminating on the postsynaptic cell body are axosomatic synapses. Axons that terminate on axons are axoaxonic synapses
] and
dendrite-to-dendrite.
[ Axons connecting dendrite to dendrite are dendrodendritic synapses. Axons which connect axon to dendrite are called axodendritic synapses
] Synapses are generally too small to be recognizable using a
light microscope
The optical microscope, also referred to as a light microscope, is a type of microscope that commonly uses visible light and a system of lenses to generate magnified images of small objects. Optical microscopes are the oldest design of microsco ...
except as points where the membranes of two cells appear to touch, but their cellular elements can be visualized clearly using an
electron microscope
An electron microscope is a microscope that uses a beam of accelerated electrons as a source of illumination. As the wavelength of an electron can be up to 100,000 times shorter than that of visible light photons, electron microscopes have a hi ...
.
Chemical synapses pass information directionally from a presynaptic cell to a postsynaptic cell and are therefore asymmetric in structure and function. The presynaptic
axon terminal
Axon terminals (also called synaptic boutons, terminal boutons, or end-feet) are distal terminations of the telodendria (branches) of an axon. An axon, also called a nerve fiber, is a long, slender projection of a nerve cell, or neuron, that condu ...
, or synaptic bouton, is a specialized area within the axon of the presynaptic cell that contains
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neuro ...
s enclosed in small membrane-bound spheres called
synaptic vesicle
In a neuron, synaptic vesicles (or neurotransmitter vesicles) store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulse ...
s (as well as a number of other supporting structures and organelles, such as
mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
and
endoplasmic reticulum
The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...
). Synaptic vesicles are docked at the presynaptic
plasma membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
at regions called
active zone
The active zone or synaptic active zone is a term first used by Couteaux and Pecot-Dechavassinein in 1970 to define the site of neurotransmitter release. Two neurons make near contact through structures called synapses allowing them to communica ...
s.
Immediately opposite is a region of the postsynaptic cell containing neurotransmitter
receptor
Receptor may refer to:
* Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...
s; for synapses between two neurons the postsynaptic region may be found on the dendrites or cell body. Immediately behind the postsynaptic membrane is an elaborate complex of interlinked proteins called the
postsynaptic density
The postsynaptic density (PSD) is a protein dense ''specialization'' attached to the postsynaptic membrane. PSDs were originally identified by electron microscopy as an electron-dense region at the membrane of a postsynaptic neuron. The PSD is in ...
(PSD).
Proteins in the PSD are involved in anchoring and trafficking neurotransmitter receptors and modulating the activity of these receptors. The receptors and PSDs are often found in specialized protrusions from the main dendritic shaft called
dendritic spine
A dendritic spine (or spine) is a small membranous protrusion from a neuron's dendrite that typically receives input from a single axon at the synapse. Dendritic spines serve as a storage site for synaptic strength and help transmit electrical si ...
s.
Synapses may be described as symmetric or asymmetric. When examined under an electron microscope, asymmetric synapses are characterized by rounded vesicles in the presynaptic cell, and a prominent postsynaptic density. Asymmetric synapses are typically excitatory. Symmetric synapses in contrast have flattened or elongated vesicles, and do not contain a prominent postsynaptic density. Symmetric synapses are typically inhibitory.
The synaptic cleft —also called synaptic gap— is a gap between the pre- and postsynaptic cells that is about 20 nm (0.02 μ) wide.
The small volume of the cleft allows neurotransmitter concentration to be raised and lowered rapidly.
An
autapse An autapse is a chemical or electrical synapse from a neuron onto itself. It can also be described as a synapse formed by the axon of a neuron on its own dendrites, ''in vivo'' or ''in vitro''.
History
The term "autapse" was first coined in 1972 ...
is a chemical (or electrical) synapse formed when the axon of one neuron synapses with its own dendrites.
Signaling in chemical synapses
Overview
Here is a summary of the sequence of events that take place in synaptic transmission from a presynaptic neuron to a postsynaptic cell. Each step is explained in more detail below. Note that with the exception of the final step, the entire process may run only a few hundred microseconds, in the fastest synapses.
#The process begins with a wave of electrochemical excitation called an
action potential
An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...
traveling along the membrane of the presynaptic cell, until it reaches the synapse.
#The electrical
depolarization
In biology, depolarization or hypopolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is esse ...
of the membrane at the synapse causes channels to open that are permeable to calcium ions.
#Calcium ions flow through the presynaptic membrane, rapidly increasing the calcium concentration in the interior.
#The high calcium concentration activates a set of calcium-sensitive proteins attached to
vesicles
Vesicle may refer to:
; In cellular biology or chemistry
* Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane
* Synaptic vesicle
; In human embryology
* Vesicle (embryology), bulge-like features o ...
that contain a
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neuro ...
chemical.
#These proteins change shape, causing the membranes of some "docked" vesicles to fuse with the membrane of the presynaptic cell, thereby opening the vesicles and dumping their neurotransmitter contents into the synaptic cleft, the narrow space between the membranes of the pre- and postsynaptic cells.
#The neurotransmitter diffuses within the cleft. Some of it escapes, but some of it binds to
chemical receptor
A chemoreceptor, also known as chemosensor, is a specialized sensory receptor which transduces a chemical substance (endogenous or induced) to generate a biological signal. This signal may be in the form of an action potential, if the chemorecept ...
molecules located on the membrane of the postsynaptic cell.
#The binding of neurotransmitter causes the receptor molecule to be ''activated'' in some way. Several types of activation are possible, as described in more detail below. In any case, this is the key step by which the synaptic process affects the behavior of the postsynaptic cell.
#Due to
thermal vibration
The term "thermal energy" is used loosely in various contexts in physics and engineering. It can refer to several different well-defined physical concepts. These include the internal energy or enthalpy of a body of matter and radiation; heat, d ...
, the motion of atoms, vibrating about their equilibrium positions in a crystalline solid, neurotransmitter molecules eventually break loose from the receptors and drift away.
#The neurotransmitter is either reabsorbed by the presynaptic cell, and then repackaged for future release, or else it is broken down metabolically.
Neurotransmitter release
![Neuro Muscular Junction](https://upload.wikimedia.org/wikipedia/commons/a/ac/Neuro_Muscular_Junction.png)
The release of a neurotransmitter is triggered by the arrival of a nerve impulse (or
action potential
An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...
) and occurs through an unusually rapid process of cellular secretion (
exocytosis
Exocytosis () is a form of active transport and bulk transport in which a cell transports molecules (e.g., neurotransmitters and proteins) out of the cell ('' exo-'' + ''cytosis''). As an active transport mechanism, exocytosis requires the use o ...
). Within the presynaptic nerve terminal,
vesicle
Vesicle may refer to:
; In cellular biology or chemistry
* Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane
* Synaptic vesicle
; In human embryology
* Vesicle (embryology), bulge-like features o ...
s containing neurotransmitter are localized near the synaptic membrane. The arriving action potential produces an influx of
calcium ions
Calcium ions (Ca2+) contribute to the physiology and biochemistry of organisms' cells. They play an important role in signal transduction pathways, where they act as a second messenger, in neurotransmitter release from neurons, in contraction of ...
through
voltage-dependent, calcium-selective ion channels at the down stroke of the action potential (tail current).
[
] Calcium ions then bind to
synaptotagmin
Synaptotagmins (SYTs) constitute a family of membrane-trafficking proteins that are characterized by an N-terminal transmembrane region (TMR), a variable linker, and two C-terminal C2 domains - C2A and C2B. There are 17 isoforms in the mammalian s ...
proteins found within the membranes of the synaptic vesicles, allowing the vesicles to fuse with the presynaptic membrane. The fusion of a vesicle is a
stochastic
Stochastic (, ) refers to the property of being well described by a random probability distribution. Although stochasticity and randomness are distinct in that the former refers to a modeling approach and the latter refers to phenomena themselv ...
process, leading to frequent failure of synaptic transmission at the very small synapses that are typical for the
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
. Large chemical synapses (e.g. the
neuromuscular junction
A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber.
It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction.
Muscles require innervation to ...
), on the other hand, have a synaptic release probability, in effect, of 1.
Vesicle fusion Vesicle fusion is the merging of a vesicle with other vesicles or a part of a cell membrane. In the latter case, it is the end stage of secretion from secretory vesicles, where their contents are expelled from the cell through exocytosis. Vesicles c ...
is driven by the action of a set of proteins in the presynaptic terminal known as
SNAREs. As a whole, the protein complex or structure that mediates the docking and fusion of presynaptic vesicles is called the active zone. The membrane added by the fusion process is later retrieved by
endocytosis
Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. E ...
and
recycled
Recycling is the process of converting waste materials into new materials and objects. The recovery of energy from waste materials is often included in this concept. The recyclability of a material depends on its ability to reacquire the p ...
for the formation of fresh neurotransmitter-filled vesicles.
An exception to the general trend of neurotransmitter release by vesicular fusion is found in the type II receptor cells of mammalian
taste bud
Taste buds contain the taste receptor cells, which are also known as gustatory cells. The taste receptors are located around the small structures known as lingual papillae, papillae found on the upper surface of the tongue, soft palate, upper e ...
s. Here the neurotransmitter
ATP is released directly from the cytoplasm into the synaptic cleft via voltage gated channels.
Receptor binding
Receptors on the opposite side of the synaptic gap bind neurotransmitter molecules. Receptors can respond in either of two general ways. First, the receptors may directly open
ligand-gated ion channel
Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in res ...
s in the postsynaptic cell membrane, causing ions to enter or exit the cell and changing the local
transmembrane potential.
The resulting change in
voltage
Voltage, also known as electric pressure, electric tension, or (electric) potential difference, is the difference in electric potential between two points. In a static electric field, it corresponds to the work needed per unit of charge to m ...
is called a
postsynaptic potential
Postsynaptic potentials are changes in the membrane potential of the postsynaptic terminal of a chemical synapse. Postsynaptic potentials are graded potentials, and should not be confused with action potentials although their function is to ini ...
. In general, the result is ''excitatory'' in the case of
depolarizing
In biology, depolarization or hypopolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is esse ...
currents, and ''inhibitory'' in the case of
hyperpolarizing currents. Whether a synapse is excitatory or inhibitory depends on what type(s) of ion channel conduct the postsynaptic current(s), which in turn is a function of the type of receptors and neurotransmitter employed at the synapse. The second way a receptor can affect membrane potential is by modulating the production of
chemical messengers inside the postsynaptic neuron. These second messengers can then amplify the inhibitory or excitatory response to neurotransmitters.
Termination
After a neurotransmitter molecule binds to a receptor molecule, it must be removed to allow for the postsynaptic membrane to continue to relay subsequent
EPSPs and/or
IPSPs. This removal can happen through one or more processes:
*The neurotransmitter may diffuse away due to thermally-induced oscillations of both it and the receptor, making it available to be broken down metabolically outside the neuron or to be reabsorbed.
[Sherwood L., stikawy (2007). Human Physiology 6e: From Cells to Systems]
*Enzymes within the subsynaptic membrane may inactivate/metabolize the neurotransmitter.
*
Reuptake
Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal (i.e., the pre-synaptic neuron at a synapse) or glial cell after it has performed its function of transm ...
pumps may actively pump the neurotransmitter back into the presynaptic
axon terminal
Axon terminals (also called synaptic boutons, terminal boutons, or end-feet) are distal terminations of the telodendria (branches) of an axon. An axon, also called a nerve fiber, is a long, slender projection of a nerve cell, or neuron, that condu ...
for reprocessing and re-release following a later action potential.
Synaptic strength
The strength of a synapse has been defined by
Sir Bernard Katz
Sir Bernard Katz, FRS (; 26 March 1911 – 20 April 2003) was a German-born British physician and biophysicist, noted for his work on nerve physiology. He shared the Nobel Prize in physiology or medicine in 1970 with Julius Axelrod and Ulf von ...
as the product of (presynaptic) release probability ''pr'', quantal size ''q'' (the postsynaptic response to the release of a single neurotransmitter vesicle, a 'quantum'), and ''n'', the number of release sites. "Unitary connection" usually refers to an unknown number of individual synapses connecting a presynaptic neuron to a postsynaptic neuron.
The amplitude of postsynaptic potentials (PSPs) can be as low as 0.4 mV to as high as 20 mV. The amplitude of a PSP can be modulated by
neuromodulators
Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a second m ...
or can change as a result of previous activity. Changes in the synaptic strength can be short-term, lasting seconds to minutes, or long-term (
long-term potentiation
In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons ...
, or LTP), lasting hours. Learning and memory are believed to result from long-term changes in synaptic strength, via a mechanism known as
synaptic plasticity
In neuroscience, synaptic plasticity is the ability of synapses to strengthen or weaken over time, in response to increases or decreases in their activity. Since memories are postulated to be represented by vastly interconnected neural circuit ...
.
Receptor desensitization
Desensitization of the postsynaptic receptors is a decrease in response to the same neurotransmitter stimulus. It means that the strength of a synapse may in effect diminish as a train of action potentials arrive in rapid succession – a phenomenon that gives rise to the so-called frequency dependence of synapses. The nervous system exploits this property for computational purposes, and can tune its synapses through such means as
phosphorylation
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...
of the proteins involved.
Synaptic plasticity
Synaptic transmission can be changed by previous activity. These changes are called synaptic plasticity and may result in either a decrease in the efficacy of the synapse, called depression, or an increase in efficacy, called potentiation. These changes can either be long-term or short-term. Forms of
short-term plasticity include
synaptic fatigue or depression and
synaptic augmentation
Augmentation is one of four components of short-term synaptic plasticity that increases the probability of releasing synaptic vesicles during and after repetitive stimulation such that
:A(t) = t)/ (0)- 1,
when all the other components of enhanc ...
. Forms of
long-term plasticity include
long-term depression
In neurophysiology, long-term depression (LTD) is an activity-dependent reduction in the efficacy of neuronal synapses lasting hours or longer following a long patterned stimulus. LTD occurs in many areas of the CNS with varying mechanisms dependi ...
and
long-term potentiation
In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons ...
. Synaptic plasticity can be either homosynaptic (occurring at a single synapse) or heterosynaptic (occurring at multiple synapses).
Homosynaptic plasticity
Homosynaptic plasticity
Homosynaptic plasticity is one type of synaptic plasticity.Purves, D., Augustine, G. J., Fitzpatrick, D., Hall, W. C., LaMantia, A. S., White, L. E. (2012). Synaptic Plasticity. In Neuroscience (5th ed.) (pp. 163-182). Sunderland, Massachusetts: Si ...
(or also homotropic modulation) is a change in the synaptic strength that results from the history of activity at a particular synapse. This can result from changes in presynaptic calcium as well as feedback onto presynaptic receptors, i.e. a form of
autocrine signaling Autocrine signaling is a form of cell signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in the cell. This can be contrasted with pa ...
. Homosynaptic plasticity can affect the number and replenishment rate of vesicles or it can affect the relationship between calcium and vesicle release. Homosynaptic plasticity can also be postsynaptic in nature. It can result in either an increase or decrease in synaptic strength.
One example is neurons of the
sympathetic nervous system
The sympathetic nervous system (SNS) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of th ...
(SNS), which release
noradrenaline
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...
, which, besides affecting postsynaptic receptors, also affects presynaptic
α2-adrenergic receptors, inhibiting further release of noradrenaline.
This effect is utilized with
clonidine
Clonidine, sold under the brand name Catapres among others, is an α2-adrenergic agonist medication used to treat high blood pressure, ADHD, drug withdrawal ( alcohol, opioids, or nicotine), menopausal flushing, diarrhea, spasticity, and c ...
to perform inhibitory effects on the SNS.
Heterosynaptic plasticity
Heterosynaptic plasticity
Synaptic plasticity refers to a chemical synapse's ability to undergo changes in strength.Purves, D., Augustine, G.J., Fitzpatrick, D., Hall, W.C., LaMantia, A.S., White, L.E. (2012). Synaptic Plasticity. In Neuroscience (5th ed.) (pp. 163-182). Su ...
(or also heterotropic modulation) is a change in synaptic strength that results from the activity of other neurons. Again, the plasticity can alter the number of vesicles or their replenishment rate or the relationship between calcium and vesicle release. Additionally, it could directly affect calcium influx. Heterosynaptic plasticity can also be postsynaptic in nature, affecting receptor sensitivity.
One example is again neurons of the
sympathetic nervous system
The sympathetic nervous system (SNS) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of th ...
, which release
noradrenaline
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...
, which, in addition, generates an inhibitory effect on presynaptic terminals of neurons of the
parasympathetic nervous system
The parasympathetic nervous system (PSNS) is one of the three divisions of the autonomic nervous system, the others being the sympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of ...
.
[
]
Integration of synaptic inputs
In general, if an excitatory synapse
An excitatory synapse is a synapse in which an action potential in a presynaptic neuron increases the probability of an action potential occurring in a postsynaptic cell. Neurons form networks through which nerve impulses travel, each neuron oft ...
is strong enough, an action potential
An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...
in the presynaptic neuron will trigger an action potential in the postsynaptic cell. In many cases the excitatory postsynaptic potential
In neuroscience, an excitatory postsynaptic potential (EPSP) is a postsynaptic potential that makes the postsynaptic neuron more likely to fire an action potential. This temporary depolarization of postsynaptic membrane potential, caused by the ...
(EPSP) will not reach the threshold for eliciting an action potential. When action potentials from multiple presynaptic neurons fire simultaneously, or if a single presynaptic neuron fires at a high enough frequency, the EPSPs can overlap and summate. If enough EPSPs overlap, the summated EPSP can reach the threshold for initiating an action potential. This process is known as summation, and can serve as a high pass filter for neurons.
On the other hand, a presynaptic neuron releasing an inhibitory neurotransmitter, such as GABA, can cause an inhibitory postsynaptic potential
An inhibitory postsynaptic potential (IPSP) is a kind of synaptic potential that makes a postsynaptic neuron less likely to generate an action potential.Purves et al. Neuroscience. 4th ed. Sunderland (MA): Sinauer Associates, Incorporated; 2008. ...
(IPSP) in the postsynaptic neuron, bringing the membrane potential
Membrane potential (also transmembrane potential or membrane voltage) is the difference in electric potential between the interior and the exterior of a biological cell. That is, there is a difference in the energy required for electric charges ...
farther away from the threshold, decreasing its excitability and making it more difficult for the neuron to initiate an action potential. If an IPSP overlaps with an EPSP, the IPSP can in many cases prevent the neuron from firing an action potential. In this way, the output of a neuron may depend on the input of many different neurons, each of which may have a different degree of influence, depending on the strength and type of synapse with that neuron. John Carew Eccles
Sir John Carew Eccles (27 January 1903 – 2 May 1997) was an Australian neurophysiologist and philosopher who won the 1963 Nobel Prize in Physiology or Medicine for his work on the synapse. He shared the prize with Andrew Huxley and Alan Lloy ...
performed some of the important early experiments on synaptic integration, for which he received the Nobel Prize for Physiology or Medicine
The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, according ...
in 1963.
Volume transmission
When a neurotransmitter is released at a synapse, it reaches its highest concentration inside the narrow space of the synaptic cleft, but some of it is certain to diffuse away before being reabsorbed or broken down. If it diffuses away, it has the potential to activate receptors that are located either at other synapses or on the membrane away from any synapse. The extrasynaptic activity of a neurotransmitter is known as ''volume transmission''. It is well established that such effects occur to some degree, but their functional importance has long been a matter of controversy.
Recent work indicates that volume transmission may be the predominant mode of interaction for some special types of neurons. In the mammalian cerebral cortex, a class of neurons called neurogliaform cells
Neurogliaform cells (NGF) are inhibitory ( GABAergic) interneurons found in the cortex and the hippocampus. NGF cells represent approximately 10% of the total hippocampal inhibitory interneuron population.
In terms of morphology, they are compar ...
can inhibit other nearby cortical neurons by releasing the neurotransmitter GABA into the extracellular space. Along the same vein, GABA released from neurogliaform cells into the extracellular space also acts on surrounding astrocyte
Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of endo ...
s, assigning a role for volume transmission in the control of ionic and neurotransmitter homeostasis. Approximately 78% of neurogliaform cell boutons do not form classical synapses. This may be the first definitive example of neurons communicating chemically where classical synapses are not present.
Relationship to electrical synapses
An electrical synapse
Electricity is the set of physical phenomena associated with the presence and motion of matter that has a property of electric charge. Electricity is related to magnetism, both being part of the phenomenon of electromagnetism, as described by ...
is an electrically conductive
In physics and electrical engineering, a conductor is an object or type of material that allows the flow of charge (electric current) in one or more directions. Materials made of metal are common electrical conductors. Electric current is gener ...
link between two abutting neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
s that is formed at a narrow gap between the pre- and postsynaptic cell
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
s, known as a gap junction
Gap junctions are specialized intercellular connections between a multitude of animal cell-types. They directly connect the cytoplasm of two cells, which allows various molecules, ions and electrical impulses to directly pass through a regulate ...
. At gap junctions, cells approach within about 3.5 nm of each other, rather than the 20 to 40 nm distance that separates cells at chemical synapses. As opposed to chemical synapses, the postsynaptic potential in electrical synapses is not caused by the opening of ion channels by chemical transmitters, but rather by direct electrical coupling between both neurons. Electrical synapses are faster than chemical synapses. Electrical synapses are found throughout the nervous system, including in the retina
The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then ...
, the reticular nucleus of the thalamus
The thalamic reticular nucleus is part of the ventral thalamus that forms a capsule around the thalamus laterally. However, recent evidence from mice and fish question this statement and define it as a dorsal thalamic structure. It is separated fro ...
, the neocortex
The neocortex, also called the neopallium, isocortex, or the six-layered cortex, is a set of layers of the mammalian cerebral cortex involved in higher-order brain functions such as sensory perception, cognition, generation of motor commands, sp ...
, and in the hippocampus
The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...
. While chemical synapses are found between both excitatory and inhibitory neurons, electrical synapses are most commonly found between smaller local inhibitory neurons. Electrical synapses can exist between two axons, two dendrites, or between an axon and a dendrite. In some fish
Fish are aquatic, craniate, gill-bearing animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish as well as various extinct related groups. Approximately 95% of li ...
and amphibian
Amphibians are tetrapod, four-limbed and ectothermic vertebrates of the Class (biology), class Amphibia. All living amphibians belong to the group Lissamphibia. They inhabit a wide variety of habitats, with most species living within terres ...
s, electrical synapses can be found within the same terminal of a chemical synapse, as in Mauthner cells.
Effects of drugs
One of the most important features of chemical synapses is that they are the site of action for the majority of psychoactive drugs
A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior.
T ...
. Synapses are affected by drugs, such as curare, strychnine, cocaine, morphine, alcohol, LSD, and countless others. These drugs have different effects on synaptic function, and often are restricted to synapses that use a specific neurotransmitter. For example, curare
Curare ( /kʊˈrɑːri/ or /kjʊˈrɑːri/; ''koo-rah-ree'' or ''kyoo-rah-ree'') is a common name for various alkaloid arrow poisons originating from plant extracts. Used as a paralyzing agent by indigenous peoples in Central and South ...
is a poison that stops acetylcholine
Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...
from depolarizing the postsynaptic membrane, causing paralysis
Paralysis (also known as plegia) is a loss of motor function in one or more muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory damage. In the United States, roughly 1 in 50 ...
. Strychnine
Strychnine (, , US chiefly ) is a highly toxic, colorless, bitter, crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine, when inhaled, swallowed, or absorbed through the eye ...
blocks the inhibitory effects of the neurotransmitter glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogeni ...
, which causes the body to pick up and react to weaker and previously ignored stimuli, resulting in uncontrollable muscle spasms
A spasm is a sudden involuntary contraction of a muscle, a group of muscles, or a hollow organ such as the bladder.
A spasmodic muscle contraction may be caused by many medical conditions, including dystonia. Most commonly, it is a muscle c ...
. Morphine
Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...
acts on synapses that use endorphin
Endorphins (contracted from endogenous morphine) are chemical signals in the brain that block the perception of pain and increase feelings of wellbeing. They are produced and stored in an area of the brain known as the pituitary gland.
Hist ...
neurotransmitters, and alcohol
Alcohol most commonly refers to:
* Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom
* Alcohol (drug), an intoxicant found in alcoholic drinks
Alcohol may also refer to:
Chemicals
* Ethanol, one of sev ...
increases the inhibitory effects of the neurotransmitter GABA. LSD
Lysergic acid diethylamide (LSD), also known colloquially as acid, is a potent psychedelic drug. Effects typically include intensified thoughts, emotions, and sensory perception. At sufficiently high dosages LSD manifests primarily mental, vi ...
interferes with synapses that use the neurotransmitter serotonin
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
. Cocaine
Cocaine (from , from , ultimately from Quechuan languages, Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly recreational drug use, used recreationally for its euphoria, euphoric effects. It is primarily obtained from t ...
blocks reuptake of dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
and therefore increases its effects.
History and etymology
During the 1950s, Bernard Katz
Sir Bernard Katz, Fellow of the Royal Society, FRS (; 26 March 1911 – 20 April 2003) was a German-born British people, British physician and biophysics, biophysicist, noted for his work on nerve physiology. He shared the Nobel Prize in Physiol ...
and Paul Fatt
Paul Fatt (13 January 1924 – 28 September 2014) was a British neuroscientist, who was a professor at University College London. With Bernard Katz, he developed the "quantal hypothesis" for neurotransmitter
A neurotransmitter is a signa ...
observed spontaneous miniature synaptic currents at the frog neuromuscular junction
A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber.
It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction.
Muscles require innervation to ...
. Based on these observations, they developed the 'quantal hypothesis' that is the basis for our current understanding of neurotransmitter release as exocytosis
Exocytosis () is a form of active transport and bulk transport in which a cell transports molecules (e.g., neurotransmitters and proteins) out of the cell ('' exo-'' + ''cytosis''). As an active transport mechanism, exocytosis requires the use o ...
and for which Katz received the Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
in 1970. In the late 1960s, Ricardo Miledi
Ricardo Miledi (15 September 1927 – 18 December 2017) was a Mexican neuroscientist known for his work deciphering the role of calcium in neurotransmitter release. He also helped to develop a technique for studying native receptors in frog oocyte ...
and Katz advanced the hypothesis that depolarization-induced influx of calcium ions triggers exocytosis
Exocytosis () is a form of active transport and bulk transport in which a cell transports molecules (e.g., neurotransmitters and proteins) out of the cell ('' exo-'' + ''cytosis''). As an active transport mechanism, exocytosis requires the use o ...
.
Sir Charles Scott Sherringtonin coined the word 'synapse' and the history of the word was given by Sherrington in a letter he wrote to John Fulton:
See also
* Acclimatisation (neurones)
*Neuroscience
Neuroscience is the scientific study of the nervous system (the brain, spinal cord, and peripheral nervous system), its functions and disorders. It is a multidisciplinary science that combines physiology, anatomy, molecular biology, development ...
*Ribbon synapse
The ribbon synapse is a type of neuronal synapse characterized by the presence of an electron-dense structure, the synaptic ribbon, that holds vesicles close to the active zone. It is characterized by a tight vesicle-calcium channel coupling that p ...
Notes
References
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External links
Synapse Review for Kids
Biologymad.com (2004)
Synapse – Cell Centered Database
Atlas of Ultrastructure Neurocytology
A great electron microscope picture gallery assembled by Kristen Harris' lab of synapses and other neuronal structures.
{{DEFAULTSORT:Chemical Synapse
Cell signaling
Signal transduction
Articles containing video clips
Neural synapse