Chemical synapse

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Artistic interpretation of the major elements in chemical synaptic transmission. An electrochemical wave called an action potential travels along the axon of a neuron. When the action potential reaches the presynaptic terminal, it provokes the release of a synaptic vesicle, secreting its quanta of neurotransmitter molecules. The neurotransmitter binds to chemical receptor molecules located in the membrane of another neuron, the postsynaptic neuron, on the opposite side of the synaptic cleft. Chemical synapse schema cropped.jpg
Artistic interpretation of the major elements in chemical synaptic transmission. An electrochemical wave called an action potential travels along the axon of a neuron. When the action potential reaches the presynaptic terminal, it provokes the release of a synaptic vesicle, secreting its quanta of neurotransmitter molecules. The neurotransmitter binds to chemical receptor molecules located in the membrane of another neuron, the postsynaptic neuron, on the opposite side of 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 system. They are crucial to the biological computations that underlie perception and thought. They allow the nervous system to connect to and control other systems of the body.

Contents

At a chemical synapse, one neuron releases neurotransmitter molecules into a small space (the synaptic cleft) that is adjacent to another neuron. The neurotransmitters are contained within small sacs called synaptic vesicles, and are released into the synaptic cleft by exocytosis. These molecules then bind to neurotransmitter receptors 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 or on some other neuroglia to terminate the action of the neurotransmitter.

The adult human brain is estimated to contain from 1014 to 5 × 1014 (100–500 trillion) synapses. [1] Every cubic millimeter of cerebral cortex contains roughly a billion (short scale, i.e. 109) of them. [2] The number of synapses in the human cerebral cortex has separately been estimated at 0.15 quadrillion (150 trillion) [3]

The word "synapse" was introduced by Sir Charles Scott Sherrington in 1897. [4] Chemical synapses are not the only type of biological synapse: electrical and immunological synapses also exist. Without a qualifier, however, "synapse" commonly refers to chemical synapses.

Structure

Diagram of a chemical synaptic connection Synapse figure.png
Diagram of a chemical synaptic connection

Synapses are functional connections between neurons, or between neurons and other types of cells. [5] [6] A typical neuron gives rise to several thousand synapses, although there are some types that make far fewer. [7] Most synapses connect axons to dendrites, [8] [9] but there are also other types of connections, including axon-to-cell-body, [10] [11] axon-to-axon, [10] [11] and dendrite-to-dendrite. [9] Synapses are generally too small to be recognizable using a light microscope except as points where the membranes of two cells appear to touch, but their cellular elements can be visualized clearly using an electron microscope.

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, or synaptic bouton, is a specialized area within the axon of the presynaptic cell that contains neurotransmitters enclosed in small membrane-bound spheres called synaptic vesicles (as well as a number of other supporting structures and organelles, such as mitochondria and endoplasmic reticulum). Synaptic vesicles are docked at the presynaptic plasma membrane at regions called active zones.

Immediately opposite is a region of the postsynaptic cell containing neurotransmitter receptors; 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 (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 spines.

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. [12] The small volume of the cleft allows neurotransmitter concentration to be raised and lowered rapidly. [13]

An autapse 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. [14]

  1. The process begins with a wave of electrochemical excitation called an action potential traveling along the membrane of the presynaptic cell, until it reaches the synapse.
  2. The electrical depolarization of the membrane at the synapse causes channels to open that are permeable to calcium ions.
  3. Calcium ions flow through the presynaptic membrane, rapidly increasing the calcium concentration in the interior.
  4. The high calcium concentration activates a set of calcium-sensitive proteins attached to vesicles that contain a neurotransmitter chemical.
  5. 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.
  6. The neurotransmitter diffuses within the cleft. Some of it escapes, but some of it binds to chemical receptor molecules located on the membrane of the postsynaptic cell.
  7. 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.
  8. Due to thermal vibration, the motion of atoms, vibrating about their equilibrium positions in a crystalline solid, neurotransmitter molecules eventually break loose from the receptors and drift away.
  9. The neurotransmitter is either reabsorbed by the presynaptic cell, and then repackaged for future release, or else it is broken down metabolically.

Neurotransmitter release

Release of neurotransmitter occurs at the end of axonal branches. Neuro Muscular Junction.png
Release of neurotransmitter occurs at the end of axonal branches.

The release of a neurotransmitter is triggered by the arrival of a nerve impulse (or action potential) and occurs through an unusually rapid process of cellular secretion (exocytosis). Within the presynaptic nerve terminal, vesicles containing neurotransmitter are localized near the synaptic membrane. The arriving action potential produces an influx of calcium ions through voltage-dependent, calcium-selective ion channels at the down stroke of the action potential (tail current). [15] Calcium ions then bind to synaptotagmin proteins found within the membranes of the synaptic vesicles, allowing the vesicles to fuse with the presynaptic membrane. [16] The fusion of a vesicle is a stochastic process, leading to frequent failure of synaptic transmission at the very small synapses that are typical for the central nervous system. Large chemical synapses (e.g. the neuromuscular junction), on the other hand, have a synaptic release probability, in effect, of 1. Vesicle fusion 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. [17] The membrane added by the fusion process is later retrieved by endocytosis and recycled 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 buds. Here the neurotransmitter ATP is released directly from the cytoplasm into the synaptic cleft via voltage gated channels. [18]

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 channels in the postsynaptic cell membrane, causing ions to enter or exit the cell and changing the local transmembrane potential. [14] The resulting change in voltage is called a postsynaptic potential. In general, the result is excitatory in the case of depolarizing 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. [14]

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:

Synaptic strength

The strength of a synapse has been defined by Bernard Katz 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. [20] The amplitude of a PSP can be modulated by neuromodulators 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, 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.

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 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. Forms of long-term plasticity include long-term depression and long-term potentiation. Synaptic plasticity can be either homosynaptic (occurring at a single synapse) or heterosynaptic (occurring at multiple synapses).

Homosynaptic plasticity

Homosynaptic plasticity (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. 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 (SNS), which release noradrenaline, which, besides affecting postsynaptic receptors, also affects presynaptic α2-adrenergic receptors, inhibiting further release of noradrenaline. [21] This effect is utilized with clonidine to perform inhibitory effects on the SNS.

Heterosynaptic plasticity

Heterosynaptic plasticity (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, which release noradrenaline, which, in addition, generates an inhibitory effect on presynaptic terminals of neurons of the parasympathetic nervous system. [21]

Integration of synaptic inputs

In general, if an excitatory synapse is strong enough, an action potential in the presynaptic neuron will trigger an action potential in the postsynaptic cell. In many cases the excitatory postsynaptic potential (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. [22]

On the other hand, a presynaptic neuron releasing an inhibitory neurotransmitter, such as GABA, can cause an inhibitory postsynaptic potential (IPSP) in the postsynaptic neuron, bringing the membrane potential 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 performed some of the important early experiments on synaptic integration, for which he received the Nobel Prize for Physiology or Medicine 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. [23] It is well established that such effects occur to some degree, but their functional importance has long been a matter of controversy. [24]

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 can inhibit other nearby cortical neurons by releasing the neurotransmitter GABA into the extracellular space. [25] Along the same vein, GABA released from neurogliaform cells into the extracellular space also acts on surrounding astrocytes, assigning a role for volume transmission in the control of ionic and neurotransmitter homeostasis. [26] 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. [25]

Relationship to electrical synapses

An electrical synapse is an electrically conductive link between two abutting neurons that is formed at a narrow gap between the pre- and postsynaptic cells, known as a gap junction. 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. [27] [28] 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. [13] Electrical synapses are found throughout the nervous system, including in the retina, the reticular nucleus of the thalamus, the neocortex, and in the hippocampus. [29] 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. [30] [31] In some fish and amphibians, electrical synapses can be found within the same terminal of a chemical synapse, as in Mauthner cells. [32]

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. 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 is a poison that stops acetylcholine from depolarizing the postsynaptic membrane, causing paralysis. Strychnine blocks the inhibitory effects of the neurotransmitter glycine, which causes the body to pick up and react to weaker and previously ignored stimuli, resulting in uncontrollable muscle spasms. Morphine acts on synapses that use endorphin neurotransmitters, and alcohol increases the inhibitory effects of the neurotransmitter GABA. LSD interferes with synapses that use the neurotransmitter serotonin. Cocaine blocks reuptake of dopamine and therefore increases its effects.

History and etymology

During the 1950s, Bernard Katz and Paul Fatt observed spontaneous miniature synaptic currents at the frog neuromuscular junction. [33] Based on these observations, they developed the 'quantal hypothesis' that is the basis for our current understanding of neurotransmitter release as exocytosis and for which Katz received the Nobel Prize in Physiology or Medicine in 1970. [34] In the late 1960s, Ricardo Miledi and Katz advanced the hypothesis that depolarization-induced influx of calcium ions triggers exocytosis.

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:

'I felt the need of some name to call the junction between nerve-cell and nerve-cell... I suggested using "syndesm"... He [ Sir Michael Foster ] consulted his Trinity friend Verrall, the Euripidean scholar, about it, and Verrall suggested "synapse" (from the Greek "clasp").'–Charles Scott Sherrington [4]

See also

Notes

  1. ↑ Drachman D (2005). "Do we have brain to spare?". Neurology. 64 (12): 2004–5. doi:10.1212/01.WNL.0000166914.38327.BB. PMID   15985565. S2CID   38482114.
  2. ↑ Alonso-Nanclares L, Gonzalez-Soriano J, Rodriguez JR, DeFelipe J (September 2008). "Gender differences in human cortical synaptic density". Proc. Natl. Acad. Sci. U.S.A. 105 (38): 14615–9. Bibcode:2008PNAS..10514615A. doi: 10.1073/pnas.0803652105 . PMC   2567215 . PMID   18779570.
  3. ↑ Brain Facts and Figures Washington University.
  4. 1 2 Cowan, W. Maxwell; Südhof, Thomas C.; Stevens, Charles F. (2003). Synapses. JHU Press. p. 11. ISBN   9780801871184 . Retrieved 9 June 2020.
  5. ↑ Rapport, Richard L. (2005). Nerve Endings: The Discovery of the Synapse. W. W. Norton & Company. pp. 1–37. ISBN   978-0-393-06019-5.
  6. ↑ Squire, Larry R.; Floyd Bloom; Nicholas Spitzer (2008). Fundamental Neuroscience. Academic Press. pp. 425–6. ISBN   978-0-12-374019-9.
  7. ↑ Hyman, Steven E.; Eric Jonathan Nestler (1993). The Molecular Foundations of Psychiatry. American Psychiatric Pub. pp. 425–6. ISBN   978-0-88048-353-7.
  8. ↑ Smilkstein, Rita (2003). We're Born to Learn: Using the Brain's Natural Learning Process to Create Today's Curriculum. Corwin Press. p. 56. ISBN   978-0-7619-4642-7.
  9. 1 2 Lytton, William W. (2002). From Computer to Brain: Foundations of Computational Neuroscience. Springer. p. 28. ISBN   978-0-387-95526-1. Axons connecting dendrite to dendrite are dendrodendritic synapses. Axons which connect axon to dendrite are called axodendritic synapses
  10. 1 2 Garber, Steven D. (2002). Biology: A Self-Teaching Guide . John Wiley and Sons. p.  175. ISBN   978-0-471-22330-6. synapses connect axons to cell body.
  11. 1 2 Weiss, Mirin; Dr Steven M. Mirin; Dr Roxanne Bartel (1994). Cocaine. American Psychiatric Pub. p. 52. ISBN   978-1-58562-138-5 . Retrieved 2008-12-26. Axons terminating on the postsynaptic cell body are axosomatic synapses. Axons that terminate on axons are axoaxonic synapses
  12. ↑ Widrow, Bernard; Kim, Youngsik; Park, Dookun; Perin, Jose Krause (2019). "Nature's Learning Rule". Artificial Intelligence in the Age of Neural Networks and Brain Computing. Elsevier. pp. 1–30. doi:10.1016/b978-0-12-815480-9.00001-3. ISBN   978-0-12-815480-9. S2CID   125516633.
  13. 1 2 Kandel, Schwartz & Jessell 2000 , p. 182
  14. 1 2 3 Bear, Mark F; Connors, Barry W; Paradiso, Michael A (2007). Neuroscience: exploring the brain . Philadelphia, PA: Lippincott Williams & Wilkins. pp.  113–118.
  15. ↑ Llinás R, Steinberg IZ, Walton K (1981). "Relationship between presynaptic calcium current and postsynaptic potential in squid giant synapse". Biophysical Journal. 33 (3): 323–351. Bibcode:1981BpJ....33..323L. doi:10.1016/S0006-3495(81)84899-0. PMC   1327434 . PMID   6261850.
  16. ↑ Chapman, Edwin R. (2002). "Synaptotagmin: A Ca2+ sensor that triggers exocytosis?". Nature Reviews Molecular Cell Biology. 3 (7): 498–508. doi:10.1038/nrm855. ISSN   1471-0080. PMID   12094216. S2CID   12384262.
  17. ↑ Craig C. Garner and Kang Shen. Structure and Function of Vertebrate and Invertebrate Active Zones. Structure and Functional Organization of the Synapse. Ed: Johannes Hell and Michael Ehlers. Springer, 2008.
  18. ↑ Romanov, Roman A.; Lasher, Robert S.; High, Brigit; Savidge, Logan E.; Lawson, Adam; Rogachevskaja, Olga A.; Zhao, Haitian; Rogachevsky, Vadim V.; Bystrova, Marina F.; Churbanov, Gleb D.; Adameyko, Igor; Harkany, Tibor; Yang, Ruibiao; Kidd, Grahame J.; Marambaud, Philippe; Kinnamon, John C.; Kolesnikov, Stanislav S.; Finger, Thomas E. (2018). "Chemical synapses without synaptic vesicles: Purinergic neurotransmission through a CALHM1 channel-mitochondrial signaling complex". Science Signaling. 11 (529): eaao1815. doi:10.1126/scisignal.aao1815. ISSN   1945-0877. PMC   5966022 . PMID   29739879.
  19. 1 2 Sherwood L., stikawy (2007). Human Physiology 6e: From Cells to Systems
  20. ↑ Díaz-Ríos M, Miller MW (June 2006). "Target-specific regulation of synaptic efficacy in the feeding central pattern generator of Aplysia: potential substrates for behavioral plasticity?". Biol. Bull. 210 (3): 215–29. doi:10.2307/4134559. JSTOR   4134559. PMID   16801496. S2CID   34154835.
  21. 1 2 Rang, H.P.; Dale, M.M.; Ritter, J.M. (2003). Pharmacology (5th ed.). Edinburgh: Churchill Livingstone. p. 129. ISBN   978-0-443-07145-4.
  22. ↑ Bruce Alberts; Alexander Johnson; Julian Lewis; Martin Raff; Keith Roberts; Peter Walter, eds. (2002). "Ch. 11. Section: Single Neurons Are Complex Computation Devices". Molecular Biology of the Cell (4th ed.). Garland Science. ISBN   978-0-8153-3218-3.
  23. ↑ Zoli M, Torri C, Ferrari R, et al. (1998). "The emergence of the volume transmission concept". Brain Res. Brain Res. Rev. 26 (2–3): 136–47. doi:10.1016/S0165-0173(97)00048-9. PMID   9651506. S2CID   20495134.
  24. ↑ Fuxe K, Dahlström A, Höistad M, et al. (2007). "From the Golgi-Cajal mapping to the transmitter-based characterization of the neuronal networks leading to two modes of brain communication: wiring and volume transmission" (PDF). Brain Res Rev. 55 (1): 17–54. doi:10.1016/j.brainresrev.2007.02.009. hdl: 10447/9980 . PMID   17433836. S2CID   1323780.
  25. 1 2 Oláh S, Füle M, Komlósi G, et al. (2009). "Regulation of cortical microcircuits by unitary GABA-mediated volume transmission". Nature. 461 (7268): 1278–81. Bibcode:2009Natur.461.1278O. doi:10.1038/nature08503. PMC   2771344 . PMID   19865171.
  26. ↑ Rózsa M, Baka J, Bordé S, Rózsa B, Katona G, Tamás G, et al. (2015). "Unitary GABAergic volume transmission from individual interneurons to astrocytes in the cerebral cortex" (PDF). Brain Structure and Function. 222 (1): 651–659. doi:10.1007/s00429-015-1166-9. PMID   26683686. S2CID   30728927.
  27. ↑ Kandel, Schwartz & Jessell 2000 , p. 176
  28. ↑ Hormuzdi et al. 2004
  29. ↑ Connors BW, Long MA (2004). "Electrical synapses in the mammalian brain". Annu. Rev. Neurosci. 27 (1): 393–418. doi:10.1146/annurev.neuro.26.041002.131128. PMID   15217338.
  30. ↑ Veruki ML, Hartveit E (December 2002). "Electrical synapses mediate signal transmission in the rod pathway of the mammalian retina". J. Neurosci. 22 (24): 10558–66. doi:10.1523/JNEUROSCI.22-24-10558.2002. PMC   6758447 . PMID   12486148.
  31. ↑ Bennett MV, Pappas GD, Aljure E, Nakajima Y (March 1967). "Physiology and ultrastructure of electrotonic junctions. II. Spinal and medullary electromotor nuclei in mormyrid fish". J. Neurophysiol. 30 (2): 180–208. doi:10.1152/jn.1967.30.2.180. PMID   4167209.
  32. ↑ Pereda AE, Rash JE, Nagy JI, Bennett MV (December 2004). "Dynamics of electrical transmission at club endings on the Mauthner cells". Brain Res. Brain Res. Rev. 47 (1–3): 227–44. CiteSeerX   10.1.1.662.9352 . doi:10.1016/j.brainresrev.2004.06.010. PMID   15572174. S2CID   9527518.
  33. ↑ Augustine, George J.; Kasai, Haruo (2007-02-01). "Bernard Katz, quantal transmitter release and the foundations of presynaptic physiology". The Journal of Physiology. 578 (Pt 3): 623–625. doi:10.1113/jphysiol.2006.123224. PMC   2151334 . PMID   17068096.
  34. ↑ "Nobel prize". British Medical Journal. 4 (5729): 190. 1970-10-24. doi:10.1136/bmj.4.5729.190. PMC   1819734 . PMID   4320287.

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Neurotransmission is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron, and bind to and react with the receptors on the dendrites of another neuron a short distance away. A similar process occurs in retrograde neurotransmission, where the dendrites of the postsynaptic neuron release retrograde neurotransmitters that signal through receptors that are located on the axon terminal of the presynaptic neuron, mainly at GABAergic and glutamatergic synapses.

<span class="mw-page-title-main">Synapse</span> Structure connecting neurons in the nervous system

In the nervous system, a synapse is a structure that allows a neuron to pass an electrical or chemical signal to another neuron or a target effector cell. Synapses can be classified as either chemical or electrical, depending on the mechanism of signal transmission between neurons. In the case of electrical synapses, neurons are coupled bidirectionally with each other through gap junctions and have a connected cytoplasmic milieu. These types of synapses are known to produce synchronous network activity in the brain, but can also result in complicated, chaotic network level dynamics. Therefore, signal directionality cannot always be defined across electrical synapses.

<span class="mw-page-title-main">Synaptic potential</span> Potential difference across the postsynaptic membrane

Synaptic potential refers to the potential difference across the postsynaptic membrane that results from the action of neurotransmitters at a neuronal synapse. In other words, it is the “incoming” signal that a neuron receives. There are two forms of synaptic potential: excitatory and inhibitory. The type of potential produced depends on both the postsynaptic receptor, more specifically the changes in conductance of ion channels in the post synaptic membrane, and the nature of the released neurotransmitter. Excitatory post-synaptic potentials (EPSPs) depolarize the membrane and move the potential closer to the threshold for an action potential to be generated. Inhibitory postsynaptic potentials (IPSPs) hyperpolarize the membrane and move the potential farther away from the threshold, decreasing the likelihood of an action potential occurring. The Excitatory Post Synaptic potential is most likely going to be carried out by the neurotransmitters glutamate and acetylcholine, while the Inhibitory post synaptic potential will most likely be carried out by the neurotransmitters gamma-aminobutyric acid (GABA) and glycine. In order to depolarize a neuron enough to cause an action potential, there must be enough EPSPs to both depolarize the postsynaptic membrane from its resting membrane potential to its threshold and counterbalance the concurrent IPSPs that hyperpolarize the membrane. As an example, consider a neuron with a resting membrane potential of -70 mV (millivolts) and a threshold of -50 mV. It will need to be raised 20 mV in order to pass the threshold and fire an action potential. The neuron will account for all the many incoming excitatory and inhibitory signals via summative neural integration, and if the result is an increase of 20 mV or more, an action potential will occur.

<span class="mw-page-title-main">Summation (neurophysiology)</span>

Summation, which includes both spatial summation and temporal summation, is the process that determines whether or not an action potential will be generated by the combined effects of excitatory and inhibitory signals, both from multiple simultaneous inputs, and from repeated inputs. Depending on the sum total of many individual inputs, summation may or may not reach the threshold voltage to trigger an action potential.

<span class="mw-page-title-main">Axon terminal</span> Nerve fiber part

Axon terminals are distal terminations of the branches of an axon. An axon, also called a nerve fiber, is a long, slender projection of a nerve cell that conducts electrical impulses called action potentials away from the neuron's cell body to transmit those impulses to other neurons, muscle cells, or glands. Most presynaptic terminals in the central nervous system are formed along the axons, not at their ends.

Cellular neuroscience is a branch of neuroscience concerned with the study of neurons at a cellular level. This includes morphology and physiological properties of single neurons. Several techniques such as intracellular recording, patch-clamp, and voltage-clamp technique, pharmacology, confocal imaging, molecular biology, two photon laser scanning microscopy and Ca2+ imaging have been used to study activity at the cellular level. Cellular neuroscience examines the various types of neurons, the functions of different neurons, the influence of neurons upon each other, and how neurons work together.

<span class="mw-page-title-main">Nonsynaptic plasticity</span> Form of neuroplasticity

Nonsynaptic plasticity is a form of neuroplasticity that involves modification of ion channel function in the axon, dendrites, and cell body that results in specific changes in the integration of excitatory postsynaptic potentials and inhibitory postsynaptic potentials. Nonsynaptic plasticity is a modification of the intrinsic excitability of the neuron. It interacts with synaptic plasticity, but it is considered a separate entity from synaptic plasticity. Intrinsic modification of the electrical properties of neurons plays a role in many aspects of plasticity from homeostatic plasticity to learning and memory itself. Nonsynaptic plasticity affects synaptic integration, subthreshold propagation, spike generation, and other fundamental mechanisms of neurons at the cellular level. These individual neuronal alterations can result in changes in higher brain function, especially learning and memory. However, as an emerging field in neuroscience, much of the knowledge about nonsynaptic plasticity is uncertain and still requires further investigation to better define its role in brain function and behavior.

In neuroscience, synaptic scaling is a form of homeostatic plasticity, in which the brain responds to chronically elevated activity in a neural circuit with negative feedback, allowing individual neurons to reduce their overall action potential firing rate. Where Hebbian plasticity mechanisms modify neural synaptic connections selectively, synaptic scaling normalizes all neural synaptic connections by decreasing the strength of each synapse by the same factor, so that the relative synaptic weighting of each synapse is preserved.

Neurotransmitters are released into a synapse in packaged vesicles called quanta. One quantum generates a miniature end plate potential (MEPP) which is the smallest amount of stimulation that one neuron can send to another neuron. Quantal release is the mechanism by which most traditional endogenous neurotransmitters are transmitted throughout the body. The aggregate sum of many MEPPs is an end plate potential (EPP). A normal end plate potential usually causes the postsynaptic neuron to reach its threshold of excitation and elicit an action potential. Electrical synapses do not use quantal neurotransmitter release and instead use gap junctions between neurons to send current flows between neurons. The goal of any synapse is to produce either an excitatory postsynaptic potential (EPSP) or an inhibitory postsynaptic potential (IPSP), which generate or repress the expression, respectively, of an action potential in the postsynaptic neuron. It is estimated that an action potential will trigger the release of approximately 20% of an axon terminal's neurotransmitter load.

Communication between neurons happens primarily through chemical neurotransmission at the synapse. Neurotransmitters are packaged into synaptic vesicles for release from the presynaptic cell into the synapse, from where they diffuse and can bind to postsynaptic receptors. While most presynaptic cells are historically thought to release one vesicle at a time per active site, more recent research has pointed towards the possibility of multiple vesicles being released from the same active site in response to an action potential.

References

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