In 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 ...
, a synapse
is a structure that permits a
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. ...
(or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell.
Synapses are essential to the transmission of nervous impulses from one neuron to another. Neurons are specialized to pass signals to individual target cells, and synapses are the means by which they do so. At a synapse, the
plasma membrane of the signal-passing neuron (the ''presynaptic'' neuron) comes into close apposition with the membrane of the target (''postsynaptic'') cell. Both the presynaptic and postsynaptic sites contain extensive arrays of
molecular machinery that link the two membranes together and carry out the signaling process. In many synapses, the presynaptic part is located on an
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 p ...
and the postsynaptic part is located on a
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 ...
or
soma
Soma may refer to:
Businesses and brands
* SOMA (architects), a New York–based firm of architects
* Soma (company), a company that designs eco-friendly water filtration systems
* SOMA Fabrications, a builder of bicycle frames and other bicycle ...
.
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 e ...
s also exchange information with the synaptic neurons, responding to synaptic activity and, in turn, regulating
neurotransmission
Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron), ...
. Synapses (at least chemical synapses) are stabilized in position by synaptic adhesion molecules (SAMs) projecting from both the pre- and post-synaptic neuron and sticking together where they overlap; SAMs may also assist in the generation and functioning of synapses.
History
Santiago Ramón y Cajal
Santiago Ramón y Cajal (; 1 May 1852 – 17 October 1934) was a Spanish neuroscientist, pathologist, and histologist specializing in neuroanatomy and the central nervous system. He and Camillo Golgi received the Nobel Prize in Physiology or Me ...
proposed that neurons are not continuous throughout the body, yet still communicate with each other, an idea known as the
neuron doctrine
The neuron doctrine is the concept that the nervous system is made up of discrete individual cells, a discovery due to decisive neuro-anatomical work of Santiago Ramón y Cajal and later presented by, among others, H. Waldeyer-Hartz. The term '' ...
. The word "synapse" was introduced in 1897 by the English neurophysiologist
Charles 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
Michael Foster's ''Textbook of Physiology''.
Sherrington struggled to find a good term that emphasized a union between two ''separate'' elements, and the actual term "synapse" was suggested by the English classical scholar
Arthur Woollgar Verrall, a friend of Foster. The word was derived from the
Greek
Greek may refer to:
Greece
Anything of, from, or related to Greece, a country in Southern Europe:
*Greeks, an ethnic group.
*Greek language, a branch of the Indo-European language family.
**Proto-Greek language, the assumed last common ancestor ...
''synapsis'' (), meaning "conjunction", which in turn derives from ( ("together") and ("to fasten"))
However, while the synaptic gap remained a theoretical construct, and sometimes reported as a discontinuity between contiguous axonal terminations and dendrites or cell bodies, histological methods using the best light microscopes of the day could not visually resolve their separation which is now known to be about 20nm. It needed the electron microscope in the 1950s to show the finer structure of the synapse with its separate, parallel pre- and postsynaptic membranes and processes, and the cleft between the two.
Chemical and electrical synapses
![Neuro Muscular Junction](https://upload.wikimedia.org/wikipedia/commons/a/ac/Neuro_Muscular_Junction.png)
There are two fundamentally different types of synapses:
* In a
chemical synapse
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 ...
, electrical activity in the presynaptic neuron is converted (via the activation of
voltage-gated calcium channels
Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (''e.g.'', muscle, glial cells, neurons, etc.) with a permeabi ...
) into the release of a chemical called a
neurotransmitter that binds to
receptors
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 n ...
located in the plasma membrane of the postsynaptic cell. The neurotransmitter may initiate an electrical response or a secondary messenger pathway that may either excite or inhibit the postsynaptic neuron. Chemical synapses can be classified according to the neurotransmitter released:
glutamatergic
Glutamatergic means "related to glutamate". A glutamatergic agent (or drug) is a chemical that directly modulates the excitatory amino acid (glutamate/aspartate) system in the body or brain. Examples include excitatory amino acid receptor agonis ...
(often excitatory),
GABAergic (often inhibitory),
cholinergic
Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word " choline" describes the various quaternary ammonium salts containing the ''N'',''N'',''N''-trimethylethanolammonium cati ...
(e.g. vertebrate
neuromuscular junction), and
adrenergic
Adrenergic means "working on adrenaline (epinephrine) or noradrenaline (norepinephrine)" (or on their receptors). When not further qualified, it is usually used in the sense of enhancing or mimicking the effects of epinephrine and norepinephrine ...
(releasing
norepinephrine
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' ...
). Because of the complexity of receptor
signal transduction, chemical synapses can have complex effects on the postsynaptic cell.
* In 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 ...
, the presynaptic and postsynaptic cell membranes are connected by special channels called
gap junctions that are capable of passing an electric current, causing voltage changes in the presynaptic cell to induce voltage changes in the postsynaptic cell. The main advantage of an electrical synapse is the rapid transfer of signals from one cell to the next.
Synaptic communication is distinct from an
ephaptic coupling
Ephaptic coupling is a form of communication within the nervous system and is distinct from direct communication systems like electrical synapses and chemical synapses. It may refer to the coupling of adjacent (touching) nerve fibers caused by the ...
, in which communication between neurons occurs via indirect electric fields.
An
autapse is a chemical or electrical synapse that forms when the axon of one neuron synapses onto dendrites of the same neuron.
Types of interfaces
Synapses can be classified by the type of cellular structures serving as the pre- and post-synaptic components. The vast majority of synapses in the mammalian nervous system are classical axo-dendritic synapses (axon synapsing upon a dendrite), however, a variety of other arrangements exist. These include but are not limited to
axo-axonic,
dendro-dendritic, axo-secretory, axo-ciliary, somato-dendritic, dendro-somatic, and somato-somatic synapses.
The axon can synapse onto a dendrite, onto a cell body, or onto another axon or axon terminal, as well as into the bloodstream or diffusely into the adjacent nervous tissue.
Role in memory
It is widely accepted that the synapse plays a role in the formation of
memory
Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembered ...
. As neurotransmitters activate receptors across the synaptic cleft, the connection between the two neurons is strengthened when both neurons are active at the same time, as a result of the receptor's signaling mechanisms. The strength of two connected neural pathways is thought to result in the storage of information, resulting in memory. This process of synaptic strengthening is known as
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 ...
.
By altering the release of neurotransmitters, the plasticity of synapses can be controlled in the presynaptic cell. The postsynaptic cell can be regulated by altering the function and number of its receptors. Changes in postsynaptic signaling are most commonly associated with a
N-methyl-d-aspartic acid
''N''-methyl--aspartic acid or ''N''-methyl--aspartate (NMDA) is an amino acid derivative that acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor. Unlike ...
receptor (NMDAR)-dependent long-term potentiation (LTP) and
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 depen ...
(LTD) due to the influx of calcium into the post-synaptic cell, which are the most analyzed forms of plasticity at excitatory synapses.
Study models
For technical reasons, synaptic structure and function have been historically studied at unusually large
model
A model is an informative representation of an object, person or system. The term originally denoted the plans of a building in late 16th-century English, and derived via French and Italian ultimately from Latin ''modulus'', a measure.
Models c ...
synapses, for example:
*
Squid giant synapse
The squid giant synapse is a chemical synapse found in squid. It is the largest chemical junction in nature.
Anatomy
The squid giant synapse (Fig 1) was first recognized by John Zachary Young in 1939. It lies in the stellate ganglion on each s ...
*
Neuromuscular junction (NMJ), a cholinergic synapse in vertebrates, glutamatergic in insects
* Ciliary calyx in the ciliary ganglion of chicks
*
Calyx of Held
The Calyx of Held is a particularly large synapse in the mammalian auditory central nervous system, so named after Hans Held who first described it in his 1893 article ''Die centrale Gehörleitung''Held, H. "Die centrale Gehörleitung" Arch. Anat ...
in the brainstem
*
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 th ...
in the retina
*
Schaffer collateral Schaffer collaterals are axon collaterals given off by CA3 pyramidal cells in the hippocampus. These collaterals project to area CA1 of the hippocampus and are an integral part of memory formation and the emotional network of the Papez circuit, and ...
synapses 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, ...
. These synapses are small, but their pre- and postsynaptic neurons are well separated (CA3 and CA1, respectively).
Synaptic polarization
The function of neurons depends upon
cell polarity. The distinctive structure of nerve cells allows
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, ...
s to travel directionally (from dendrites to cell body down the axon), and for these signals to then be received and carried on by post-synaptic neurons or received by effector cells. Nerve cells have long been used as models for cellular polarization, and of particular interest are the mechanisms underlying the polarized localization of synaptic molecules.
PIP2
Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)''P''2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)''P''2 is enriched at the plasma membrane where it is a substrate for a number of ...
signaling regulated by
IMPase plays an integral role in synaptic polarity.
Phosphoinositides
Phosphatidylinositol (or Inositol Phospholipid) consists of a family of lipids as illustrated on the right, where red is x, blue is y, and black is z, in the context of independent variation, a class of the phosphatidylglycerides. In such molecul ...
(
PIP, PIP2, and
PIP3
Phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)''P''3), abbreviated PIP3, is the product of the class I phosphoinositide 3-kinases (PI 3-kinases) phosphorylation of phosphatidylinositol (4,5)-bisphosphate (PIP2). It is a phospholipid th ...
) are molecules that have been shown to affect neuronal polarity. A gene (''ttx-7'') was identified in ''
Caenorhabditis elegans'' that encodes ''myo''-inositol monophosphatase (IMPase), an enzyme that produces
inositol by
dephosphorylating inositol phosphate
Inositol phosphates are a group of mono- to hexaphosphorylated inositols. They play crucial roles in diverse cellular functions, such as cell growth, apoptosis, cell migration, endocytosis, and cell differentiation.
The group comprises:
* inosito ...
. Organisms with mutant ''ttx-7'' genes demonstrated behavioral and localization defects, which were rescued by expression of IMPase. This led to the conclusion that IMPase is required for the correct localization of synaptic protein components.
The ''egl-8'' gene encodes a homolog of
phospholipase Cβ (PLCβ), an enzyme that cleaves PIP2. When ''ttx-7'' mutants also had a mutant ''egl-8'' gene, the defects caused by the faulty ''ttx-7'' gene were largely reversed. These results suggest that PIP2 signaling establishes polarized localization of synaptic components in living neurons.
Presynaptic modulation
Modulation of neurotransmitter release by
G-protein-coupled receptors
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...
(GPCRs) is a prominent presynaptic mechanism for regulation of
synaptic transmission. The activation of GPCRs located at the presynaptic terminal, can decrease the probability of neurotransmitter release. This presynaptic depression involves activation of
Gi/o-type
G-proteins
G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their ac ...
that mediate different inhibitory mechanisms, including inhibition of
voltage-gated calcium channel
Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (''e.g.'', muscle, glial cells, neurons, etc.) with a permeabili ...
s, activation of
potassium channel
Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of c ...
s, and direct inhibition of the
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 ...
process.
Endocannabinoids
Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tet ...
, synthesized in and released from postsynaptic
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. ...
al elements, and their cognate
receptors
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 n ...
, including the (GPCR)
CB1 receptor
Cannabinoid receptor type 1 (CB1), also known as cannabinoid receptor 1, is a G protein-coupled cannabinoid receptor that in humans is encoded by the ''CNR1'' gene. The human CB1 receptor is expressed in the peripheral nervous system and centr ...
, located at the presynaptic terminal, are involved in this modulation by an
retrograde signaling
Retrograde signaling in biology is the process where a signal travels backwards from a target source to its original source. For example, the nucleus of a cell is the original source for creating signaling proteins. During retrograde signaling, ins ...
process, in which these compounds are synthesized in and released from postsynaptic neuronal elements, and travel back to the presynaptic terminal to act on the CB1 receptor for short-term (STD) or long-term synaptic depression (LTD), that cause a short or long lasting decrease in neurotransmitter release.
Additional images
Image:Synapse figure.png, Diagram of the synapse. Please se
learnbio.org
for interactive version
Image:Neuron synapse.svg, A typical central nervous system synapse
Image:Active zone3.JPG, The synapse and synaptic vesicle cycle
Image:Chemical synapse schema cropped.jpg, Major elements in chemical synaptic transmission
See also
*
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 ...
*
Autapse
*
Exocytosis
*
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 syna ...
*
Neurotransmitter vesicle
*
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 ...
*
Synaptopathy
A synaptopathy is a disease of the brain, spinal cord or peripheral nervous system relating to the dysfunction of synapses. This can arise as a result of a mutation in a gene encoding a synaptic protein such as an ion channel, neurotransmitter ...
References
{{Authority control
Signal transduction