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Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called
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 are released by the
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 ...
of 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. N ...
(the presynaptic neuron), and bind to and react with the
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 ...
on the
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 of another neuron (the postsynaptic neuron) a short distance away. A similar process occurs in
retrograde neurotransmission 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 ...
, where the dendrites of the postsynaptic neuron release retrograde neurotransmitters (e.g.,
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 response to a rise in
intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...
levels) that signal through receptors that are located on the axon terminal of the presynaptic neuron, mainly at GABAergic and
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 agonist ...
synapse In the nervous system, a synapse is a structure that permits a neuron (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 ...
s.
Figure 1: Schematic of brain CB1 expression and orexinergic neurons expressing OX1 (HcrtR1) or OX2 (HcrtR2)
br
Figure 2: Synaptic signaling mechanisms in cannabinoid and orexin systems
br
Figure 3: Schematic of brain pathways involved in food intake
/ref> Neurotransmission is regulated by several different factors: the availability and rate-of-synthesis of the neurotransmitter, the release of that neurotransmitter, the baseline activity of the postsynaptic cell, the number of available postsynaptic receptors for the neurotransmitter to bind to, and the subsequent removal or deactivation of the neurotransmitter by enzymes or presynaptic reuptake. In response to a threshold
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, ...
or graded electrical potential, a neurotransmitter is released at the
presynaptic In the nervous system, a synapse is a structure that permits a neuron (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 ...
terminal Terminal may refer to: Computing Hardware * Terminal (electronics), a device for joining electrical circuits together * Terminal (telecommunication), a device communicating over a line * Computer terminal, a set of primary input and output dev ...
. The released neurotransmitter may then move across the synapse to be detected by and bind with receptors in the postsynaptic neuron. Binding of neurotransmitters may influence the postsynaptic neuron in either an
inhibitory 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. ...
or
excitatory 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 ...
way. The binding of neurotransmitters to receptors in the postsynaptic neuron can trigger either short term changes, such as changes in the membrane potential called
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 ...
s, or longer term changes by the activation of signaling cascades. Neurons form complex biological neural networks through which nerve impulses (action potentials) travel. Neurons do not touch each other (except in the case of 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 ...
through 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 ...
); instead, neurons interact at close contact points called synapses. A neuron transports its information by way of an action potential. When the nerve impulse arrives at the synapse, it may cause the release of neurotransmitters, which influence another (postsynaptic) neuron. The postsynaptic neuron may receive inputs from many additional neurons, both excitatory and inhibitory. The excitatory and inhibitory influences are summed, and if the net effect is inhibitory, the neuron will be less likely to "fire" (i.e., generate an action potential), and if the net effect is excitatory, the neuron will be more likely to fire. How likely a neuron is to fire depends on how far its membrane potential is from the
threshold potential In electrophysiology, the threshold potential is the critical level to which a membrane potential must be depolarized to initiate an action potential. In neuroscience, threshold potentials are necessary to regulate and propagate signaling in both ...
, the voltage at which an action potential is triggered because enough voltage-dependent
sodium channel Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the channel ...
s are activated so that the net inward sodium current exceeds all outward currents. Excitatory inputs bring a neuron closer to threshold, while inhibitory inputs bring the neuron farther from threshold. An action potential is an "all-or-none" event; neurons whose membranes have not reached threshold will not fire, while those that do must fire. Once the action potential is initiated (traditionally at the
axon hillock The axon hillock is a specialized part of the cell body (or soma) of a neuron that connects to the axon. It can be identified using light microscopy from its appearance and location in a neuron and from its sparse distribution of Nissl substance. ...
), it will propagate along the axon, leading to release of neurotransmitters at the
synaptic bouton 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 ...
to pass along information to yet another adjacent neuron.


Stages in neurotransmission at the synapse

# Synthesis of the neurotransmitter. This can take place in the cell body, in the axon, or in the
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 ...
. # Storage of the neurotransmitter in storage granules or vesicles in the axon terminal. # Calcium enters the axon terminal during an action potential, causing
release Release may refer to: * Art release, the public distribution of an artistic production, such as a film, album, or song * Legal release, a legal instrument * News release, a communication directed at the news media * Release (ISUP), a code to iden ...
of the neurotransmitter into the synaptic cleft. # After its release, the transmitter binds to and activates a receptor in the postsynaptic membrane. # Deactivation of the neurotransmitter. The neurotransmitter is either destroyed enzymatically, or taken back into the terminal from which it came, where it can be reused, or degraded and removed.


General description

Neurotransmitters are spontaneously packed in vesicles and released in individual quanta-packets independently of presynaptic action potentials. This slow release is detectable and produces micro-inhibitory or micro-excitatory effects on the postsynaptic neuron. An action potential briefly amplifies this process. Neurotransmitters containing vesicles cluster around active sites, and after they have been released may be recycled by one of three proposed mechanisms. The first proposed mechanism involves partial opening and then re-closing of the vesicle. The second two involve the full fusion of the vesicle with the membrane, followed by recycling, or recycling into the endosome. Vesicular fusion is driven largely by the concentration of calcium in micro domains located near calcium channels, allowing for only microseconds of neurotransmitter release, while returning to normal calcium concentration takes a couple of hundred of microseconds. The vesicle exocytosis is thought to be driven by a protein complex called
SNARE SNARE proteins – " SNAP REceptor" – are a large protein family consisting of at least 24 members in yeasts, more than 60 members in mammalian cells, and some numbers in plants. The primary role of SNARE proteins is to mediate vesicle fu ...
, that is the target for botulinum toxins. Once released, a neurotransmitter enters the synapse and encounters receptors. Neurotransmitter receptors can either be ionotropic or g protein coupled. Ionotropic receptors allow for ions to pass through when agonized by a ligand. The main model involves a receptor composed of multiple subunits that allow for coordination of ion preference. G protein coupled receptors, also called metabotropic receptors, when bound to by a ligand undergo conformational changes yielding in intracellular response. Termination of neurotransmitter activity is usually done by a transporter, however enzymatic deactivation is also plausible.


Summation

Each neuron connects with numerous other neurons, receiving numerous impulses from them. Summation is the adding together of these impulses at the axon hillock. If the neuron only gets excitatory impulses, it will generate an action potential. If instead the neuron gets as many inhibitory as excitatory impulses, the inhibition cancels out the excitation and the nerve impulse will stop there. Action potential generation is proportionate to the probability and pattern of neurotransmitter release, and to postsynaptic receptor sensitization. Spatial summation means that the effects of impulses received at different places on the neuron add up, so that the neuron may fire when such impulses are received simultaneously, even if each impulse on its own would not be sufficient to cause firing. Temporal summation means that the effects of impulses received at the same place can add up if the impulses are received in close temporal succession. Thus the neuron may fire when multiple impulses are received, even if each impulse on its own would not be sufficient to cause firing.


Convergence and divergence

Neurotransmission implies both a convergence and a divergence of information. First one neuron is influenced by many others, resulting in a convergence of input. When the neuron fires, the signal is sent to many other neurons, resulting in a divergence of output. Many other neurons are influenced by this neuron.


Cotransmission

Cotransmission is the release of several types of neurotransmitters from a single
nerve terminal A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system. A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the e ...
. At the nerve terminal, neurotransmitters are present within 35–50 nm membrane-encased vesicles 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. To release neurotransmitters, the synaptic vesicles transiently dock and fuse at the base of specialized 10–15 nm cup-shaped
lipoprotein A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid (also known as fat) molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, sur ...
structures at the presynaptic membrane called porosomes. The neuronal porosome
proteome The proteome is the entire set of proteins that is, or can be, expressed by a genome, cell, tissue, or organism at a certain time. It is the set of expressed proteins in a given type of cell or organism, at a given time, under defined conditions. ...
has been solved, providing the molecular architecture and the complete composition of the machinery. Recent studies in a myriad of systems have shown that most, if not all, neurons release several different chemical messengers. Cotransmission allows for more complex effects at postsynaptic receptors, and thus allows for more complex communication to occur between neurons. In modern neuroscience, neurons are often classified by their cotransmitter. For example, striatal "GABAergic neurons" utilize
opioid peptide Opioid peptides are peptides that bind to opioid receptors in the brain; opiates and opioids mimic the effect of these peptides. Such peptides may be produced by the body itself, for example endorphins. The effects of these peptides vary, but t ...
s or
substance P Substance P (SP) is an undecapeptide (a peptide composed of a chain of 11 amino acid residues) and a member of the tachykinin neuropeptide family. It is a neuropeptide, acting as a neurotransmitter and as a neuromodulator. Substance P and its clo ...
as their primary cotransmitter. Some neurons can release at least two neurotransmitters at the same time, the other being a cotransmitter, in order to provide the stabilizing negative feedback required for meaningful encoding, in the absence of inhibitory
interneuron Interneurons (also called internuncial neurons, relay neurons, association neurons, connector neurons, intermediate neurons or local circuit neurons) are neurons that connect two brain regions, i.e. not direct motor neurons or sensory neurons. I ...
s. Examples include: * GABA
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 ...
co-release. *
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 ...
glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...
co-release. *
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 ...
(Ach)–glutamate co-release. * ACh–
vasoactive intestinal peptide Vasoactive intestinal peptide, also known as vasoactive intestinal polypeptide or VIP, is a peptide hormone that is vasoactive in the intestine. VIP is a peptide of 28 amino acid residues that belongs to a glucagon/secretin superfamily, the lig ...
(VIP) co-release. * ACh–
calcitonin gene-related peptide Calcitonin gene-related peptide (CGRP) is a member of the calcitonin family of peptides consisting of calcitonin, amylin, adrenomedullin, adrenomedullin 2 ( intermedin) and calcitonin‑receptor‑stimulating peptide. Calcitonin is mainly produ ...
(CGRP) co-release. * Glutamate–
dynorphin Dynorphins (Dyn) are a class of opioid peptides that arise from the precursor protein prodynorphin. When prodynorphin is cleaved during processing by proprotein convertase 2 (PC2), multiple active peptides are released: dynorphin A, dynorphin B, a ...
co-release (in
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 ...
).
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'', ...
and ATP are sympathetic co-transmitters. It is found that the endocannabinoid anadamide and the
cannabinoid 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 ...
WIN 55,212-2 WIN 55,212-2 is a chemical described as an aminoalkylindole derivative, which produces effects similar to those of cannabinoids such as tetrahydrocannabinol (THC) but has an entirely different chemical structure. WIN 55,212-2 is a potent canna ...
can modify the overall response to sympathetic nerve stimulation, and indicate that prejunctional CB1 receptors mediate the sympatho-inhibitory action. Thus cannabinoids can inhibit both the noradrenergic and purinergic components of sympathetic neurotransmission. One unusual pair of co-transmitters is GABA and glutamate which are released from the same axon terminals of neurons originating from the
ventral tegmental area The ventral tegmental area (VTA) (tegmentum is Latin for ''covering''), also known as the ventral tegmental area of Tsai, or simply ventral tegmentum, is a group of neurons located close to the midline on the floor of the midbrain. The VTA is the ...
(VTA),
internal globus pallidus The internal globus pallidus (GPi or medial globus pallidus; in rodents its homologue is known as the entopeduncular nucleus) and the external globus pallidus (GPe) make up the globus pallidus. The GPi is one of the output nuclei of the basal gang ...
, and
supramammillary nucleus The supramammillary nucleus (SuM), or supramammillary area, is a thin layer of cells in the brain that lies above the mammillary bodies. It can be considered part of the hypothalamus and diencephalon. The nucleus can be divided into medial and later ...
. The former two project to the
habenula In neuroanatomy, habenula (diminutive of Latin ''habena'' meaning rein) originally denoted the stalk of the pineal gland (pineal habenula; pedunculus of pineal body), but gradually came to refer to a neighboring group of nerve cells with which the ...
whereas the projections from the supramammillary nucleus are known to target the
dentate gyrus The dentate gyrus (DG) is part of the hippocampal formation in the temporal lobe of the brain, which also includes the hippocampus and the subiculum. The dentate gyrus is part of the hippocampal trisynaptic circuit and is thought to contribute ...
of the hippocampus.


Genetic association

Neurotransmission is genetically associated with other characteristics or features. For example, enrichment analyses of different signaling pathways led to the discovery of a genetic association with intracranial volume.


See also

*
Autoreceptor An autoreceptor is a type of receptor located in the membranes of nerve cells. It serves as part of a negative feedback loop in signal transduction. It is only sensitive to the neurotransmitters or hormones released by the neuron on which the au ...
* Biological neuron model § Synaptic transmission *
Electrophysiology Electrophysiology (from Greek , ''ēlektron'', "amber" etymology of "electron"">Electron#Etymology">etymology of "electron" , ''physis'', "nature, origin"; and , '' -logia'') is the branch of physiology that studies the electrical properties of b ...
*
G protein-coupled receptor 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 ...
*
Molecular neuropharmacology Neuropharmacology is the study of how drugs affect function in the nervous system, and the neural mechanisms through which they influence behavior. There are two main branches of neuropharmacology: behavioral and molecular. Behavioral neuropharmac ...
* Neuromuscular transmission *
Neuropsychopharmacology Neuropsychopharmacology, an interdisciplinary science related to psychopharmacology (study of effects of drugs on the mind) and fundamental neuroscience, is the study of the neural mechanisms that drugs act upon to influence behavior. It entails ...


References

{{Reflist, 30em


External links


Historical evolution of the neurotransmission concept
Neurophysiology Molecular neuroscience