Editing Synaptic plasticity

{{short description|Ability of a synapse to strengthen or weaken over time according to its activity}}
{{About|synaptic plasticity|the role of synapse formation and stabilization in plasticity|Synaptic stabilization|the general concept of brain plasticity|neuroplasticity}}

[[File:Synaptic_Plasticity_Rule.png|thumb|Synaptic plasticity rule for gradient estimation by dynamic perturbation of conductances]]
In [[neuroscience]], '''synaptic plasticity''' is the ability of [[synapses]] to [[Chemical synapse#Synaptic strength|strengthen or weaken]] over time, in response to increases or decreases in their activity.<ref>{{cite journal | vauthors = Hughes JR | title = Post-tetanic potentiation | journal = Physiological Reviews | volume = 38 | issue = 1 | pages = 91–113 | date = January 1958 | pmid = 13505117 | doi = 10.1152/physrev.1958.38.1.91 }}</ref> Since [[memory|memories]] are postulated to be represented by vastly interconnected [[neural circuit]]s in the [[brain]], synaptic plasticity is one of the important neurochemical foundations of [[learning]] and [[memory]] (''see [[Hebbian theory]]'').

Plastic change often results from the alteration of the number of [[neurotransmitter receptor]]s located on a synapse.<ref name="NewT">{{cite journal | vauthors = Gerrow K, Triller A | title = Synaptic stability and plasticity in a floating world | journal = Current Opinion in Neurobiology | volume = 20 | issue = 5 | pages = 631–9 | date = October 2010 | pmid = 20655734 | doi = 10.1016/j.conb.2010.06.010 | s2cid = 7988672 }}</ref> There are several underlying mechanisms that cooperate to achieve synaptic plasticity, including changes in the quantity of [[neurotransmitter]]s released into a synapse and changes in how effectively cells respond to those neurotransmitters.<ref>
{{cite journal | vauthors = Gaiarsa JL, Caillard O, Ben-Ari Y | title = Long-term plasticity at GABAergic and glycinergic synapses: mechanisms and functional significance | journal = Trends in Neurosciences | volume = 25 | issue = 11 | pages = 564–70 | date = November 2002 | pmid = 12392931 | doi = 10.1016/S0166-2236(02)02269-5 | s2cid = 17365083 }}</ref> Synaptic plasticity in both [[Excitatory synapse|excitatory]] and [[Inhibitory synapse|inhibitory]] synapses has been found to be dependent upon [[postsynaptic]] [[calcium]] release.<ref name="NewT"/>

==Historical discoveries==
In 1973, [[Terje Lømo]] and [[Tim Bliss]] first described the now widely studied phenomenon of [[long-term potentiation]] (LTP) in a publication in the ''Journal of Physiology''. The experiment described was conducted on the synapse between the [[perforant path]] and [[dentate gyrus]] in the [[Hippocampus|hippocampi]] of anaesthetised rabbits. They were able to show a burst of tetanic (100&nbsp;Hz) stimulus on perforant path fibres led to a dramatic and long-lasting augmentation in the post-synaptic response of cells onto which these fibres synapse in the dentate gyrus. In the same year, the pair published very similar data recorded from awake rabbits. This discovery was of particular interest due to the proposed role of the hippocampus in certain forms of memory.

==Biochemical mechanisms==
Two molecular mechanisms for synaptic plasticity involve the [[NMDA]] and [[AMPA]] glutamate receptors. Opening of NMDA channels (which relates to the level of cellular [[depolarization]]) leads to a rise in post-synaptic Ca<sup>2+</sup> concentration and this has been linked to long-term potentiation, LTP (as well as to protein [[kinase]] activation); strong depolarization of the post-synaptic cell completely displaces the [[magnesium]] ions that block NMDA ion channels and allows calcium ions to enter a cell – probably causing LTP, while weaker depolarization only partially displaces the Mg<sup>2+</sup> ions, resulting in less Ca<sup>2+</sup> entering the post-synaptic neuron and lower intracellular Ca<sup>2+</sup> concentrations (which activate protein phosphatases and induce [[long-term depression]], LTD).<ref>Bear MF, Connors BW, and Paradisio MA. 2007. Neuroscience: Exploring the Brain, 3rd ed. Lippincott, Williams & Wilkins</ref>

These activated protein kinases serve to phosphorylate post-synaptic excitatory receptors (e.g. [[AMPA receptor]]s), improving cation conduction, and thereby potentiating the synapse. Also, these signals recruit additional receptors into the post-synaptic membrane, stimulating the production of a modified receptor type, thereby facilitating an influx of calcium. This in turn increases post-synaptic excitation by a given pre-synaptic stimulus. This process can be reversed via the activity of protein phosphatases, which act to dephosphorylate these cation channels.<ref>{{cite journal | vauthors = Soderling TR, Derkach VA | title = Postsynaptic protein phosphorylation and LTP | journal = Trends in Neurosciences | volume = 23 | issue = 2 | pages = 75–80 | date = February 2000 | pmid = 10652548 | doi = 10.1016/S0166-2236(99)01490-3 | s2cid = 16733526 }}</ref>

The second mechanism depends on a [[second messenger]] cascade regulating [[Transcription (genetics)|gene transcription]] and changes in the levels of key proteins such as [[CaMKII]] and PKAII. Activation of the second messenger pathway leads to increased levels of CaMKII and PKAII within the [[dendritic spine]]. These protein kinases have been linked to growth in dendritic spine volume and LTP processes such as the addition of AMPA receptors to the [[plasma membrane]] and phosphorylation of ion channels for enhanced permeability.<ref name="Haining09">
{{cite journal | vauthors = Zhong H, Sia GM, Sato TR, Gray NW, Mao T, Khuchua Z, Huganir RL, Svoboda K | display-authors = 6 | title = Subcellular dynamics of type II PKA in neurons | journal = Neuron | volume = 62 | issue = 3 | pages = 363–74 | date = May 2009 | pmid = 19447092 | pmc = 2702487 | doi = 10.1016/j.neuron.2009.03.013 }}</ref> Localization or compartmentalization of activated proteins occurs in the presence of their given stimulus which creates local effects in the dendritic spine. Calcium influx from NMDA receptors is necessary for the activation of CaMKII. This activation is localized to spines with focal stimulation and is inactivated before spreading to adjacent spines or the shaft, indicating an important mechanism of LTP in that particular changes in protein activation can be localized or compartmentalized to enhance the responsivity of single dendritic spines. Individual dendritic spines are capable of forming unique responses to presynaptic cells.<ref name="Seok-Jin09">
{{cite journal | vauthors = Lee SJ, Escobedo-Lozoya Y, Szatmari EM, Yasuda R | title = Activation of CaMKII in single dendritic spines during long-term potentiation | journal = Nature | volume = 458 | issue = 7236 | pages = 299–304 | date = March 2009 | pmid = 19295602 | pmc = 2719773 | doi = 10.1038/nature07842 | bibcode = 2009Natur.458..299L }}</ref> This second mechanism can be triggered by [[protein phosphorylation]] but takes longer and lasts longer, providing the mechanism for long-lasting memory storage. The duration of the LTP can be regulated by breakdown of these [[second messenger]]s. [[Phosphodiesterase]], for example, breaks down the secondary messenger [[Cyclic adenosine monophosphate|cAMP]], which has been implicated in increased AMPA receptor synthesis in the post-synaptic neuron {{Citation needed|date=December 2011}}.

Long-lasting changes in the efficacy of synaptic connections ([[long-term potentiation]], or LTP) between two neurons can involve the making and breaking of synaptic contacts. Genes such as activin ß-A, which encodes a subunit of [[activin A]], are up-regulated during early stage LTP. The activin molecule modulates the actin dynamics in dendritic spines through the [[Mitogen-activated protein kinase|MAP-kinase pathway]]. By changing the [[F-actin]] [[cytoskeletal]] structure of dendritic spines, spine necks are lengthened producing increased electrical isolation.<ref>{{cite journal | vauthors = Araya R, Jiang J, Eisenthal KB, Yuste R | title = The spine neck filters membrane potentials | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 47 | pages = 17961–6 | date = November 2006 | pmid = 17093040 | pmc = 1693855 | doi = 10.1073/pnas.0608755103 | bibcode = 2006PNAS..10317961A | doi-access = free }}</ref> The end result is long-term maintenance of LTP.<ref name="Synapse">{{cite journal | vauthors = Shoji-Kasai Y, Ageta H, Hasegawa Y, Tsuchida K, Sugino H, Inokuchi K | title = Activin increases the number of synaptic contacts and the length of dendritic spine necks by modulating spinal actin dynamics | journal = Journal of Cell Science | volume = 120 | issue = Pt 21 | pages = 3830–7 | date = November 2007 | pmid = 17940062 | doi = 10.1242/jcs.012450 | doi-access = free }}</ref>

The number of [[ion channel]]s on the post-synaptic membrane affects the strength of the synapse.<ref>
{{cite journal | vauthors = Debanne D, Daoudal G, Sourdet V, Russier M | title = Brain plasticity and ion channels | journal = Journal of Physiology, Paris | volume = 97 | issue = 4–6 | pages = 403–14 | year = 2003 | pmid = 15242652 | doi = 10.1016/j.jphysparis.2004.01.004 | s2cid = 19116187 }}</ref> Research suggests that the density of receptors on post-synaptic membranes changes, affecting the neuron's excitability in response to stimuli. In a dynamic process that is maintained in equilibrium, [[NMDA receptor|N-methyl D-aspartate receptor (NMDA receptor)]] and AMPA receptors are added to the membrane by [[exocytosis]] and removed by [[endocytosis]].<ref name="Shi99">
{{cite journal |author6-link=Karel Svoboda (scientist)| vauthors = Shi SH, Hayashi Y, Petralia RS, Zaman SH, Wenthold RJ, Svoboda K, Malinow R | title = Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation | journal = Science | volume = 284 | issue = 5421 | pages = 1811–6 | date = June 1999 | pmid = 10364548 | doi = 10.1126/science.284.5421.1811 | citeseerx = 10.1.1.376.3281 }}</ref><ref name="Song02">
{{cite journal | vauthors = Song I, Huganir RL | title = Regulation of AMPA receptors during synaptic plasticity | journal = Trends in Neurosciences | volume = 25 | issue = 11 | pages = 578–88 | date = November 2002 | pmid = 12392933 | doi = 10.1016/S0166-2236(02)02270-1 | s2cid = 1993509 }}</ref><ref name="PO05">{{cite journal | vauthors = Pérez-Otaño I, Ehlers MD | title = Homeostatic plasticity and NMDA receptor trafficking | journal = Trends in Neurosciences | volume = 28 | issue = 5 | pages = 229–38 | date = May 2005 | pmid = 15866197 | doi = 10.1016/j.tins.2005.03.004 | s2cid = 22901201 | url = http://www.psychiatry.wustl.edu/zorumski/journal%20club/Perez-Otano%20and%20Ehlers%209_23.pdf | access-date = 2007-06-08 | url-status = dead | archive-url = https://web.archive.org/web/20110720121632/http://www.psychiatry.wustl.edu/zorumski/journal%20club/Perez-Otano%20and%20Ehlers%209_23.pdf | archive-date = July 20, 2011 }}</ref> These processes, and by extension the number of receptors on the membrane, can be altered by synaptic activity.<ref name="Shi99" /><ref name="PO05" /> Experiments have shown that AMPA receptors are delivered to the synapse through vesicular [[membrane fusion]] with the postsynaptic membrane via the protein kinase CaMKII, which is activated by the influx of calcium through NMDA receptors. CaMKII also improves AMPA ionic conductance through phosphorylation.<ref name="Bear_2007">{{cite book | vauthors = Bear MF | author-link = Mark F. Bear | title = Neuroscience: Exploring the Brain | url = https://archive.org/details/neuroscienceexpl00mark | url-access = registration | publisher = [[Lippincott Williams & Wilkins]] | series = Third Edition | year =2007 | pages =[https://archive.org/details/neuroscienceexpl00mark/page/779 779] | isbn = 978-0-7817-6003-4}}</ref>
When there is high-frequency NMDA receptor activation, there is an increase in the expression of a protein [[PSD-95]] that increases synaptic capacity for AMPA receptors.<ref name="stabilization_plasticity">
{{cite journal | vauthors = Meyer D, Bonhoeffer T, Scheuss V | title = Balance and stability of synaptic structures during synaptic plasticity | journal = Neuron | volume = 82 | issue = 2 | pages = 430–43 | date = April 2014 | pmid = 24742464 | doi = 10.1016/j.neuron.2014.02.031 | doi-access = free }}</ref> This is what leads to a long-term increase in AMPA receptors and thus synaptic strength and plasticity.

If the strength of a synapse is only reinforced by stimulation or weakened by its lack, a [[positive feedback loop]] will develop, causing some cells never to fire and some to fire too much. But two regulatory forms of plasticity, called scaling and [[metaplasticity]], also exist to provide [[negative feedback]].<ref name="PO05" /> Synaptic scaling is a primary mechanism by which a neuron is able to stabilize firing rates up or down.<ref>
{{cite journal | vauthors = Desai NS, Cudmore RH, Nelson SB, Turrigiano GG | title = Critical periods for experience-dependent synaptic scaling in visual cortex | journal = Nature Neuroscience | volume = 5 | issue = 8 | pages = 783–9 | date = August 2002 | pmid = 12080341 | doi = 10.1038/nn878 | s2cid = 17747903 }}</ref>
  
[[Synaptic scaling]] serves to maintain the strengths of synapses relative to each other, lowering amplitudes of small [[excitatory postsynaptic potential]]s in response to continual excitation and raising them after prolonged blockage or inhibition.<ref name="PO05" /> This effect occurs gradually over hours or days, by changing the numbers of [[NMDA receptor]]s at the synapse (Pérez-Otaño and Ehlers, 2005). [[Metaplasticity]] varies the threshold level at which plasticity occurs, allowing integrated responses to synaptic activity spaced over time and preventing saturated states of LTP and LTD. Since LTP and LTD ([[long-term depression]]) rely on the influx of [[Calcium in biology|Ca<sup>2+</sup>]] through NMDA channels, metaplasticity may be due to changes in NMDA receptors, altered calcium buffering, altered states of kinases or phosphatases and a priming of protein synthesis machinery.<ref name="Abraham97">{{cite journal | vauthors = Abraham WC, Tate WP | title = Metaplasticity: a new vista across the field of synaptic plasticity | journal = Progress in Neurobiology | volume = 52 | issue = 4 | pages = 303–23 | date = July 1997 | pmid = 9247968 | doi = 10.1016/S0301-0082(97)00018-X | s2cid = 33285995 }}</ref> Synaptic scaling is a primary mechanism by which a neuron to be selective to its varying inputs.<ref name="Abbot2000">{{cite journal | vauthors = Abbott LF, Nelson SB | title = Synaptic plasticity: taming the beast | journal = Nature Neuroscience | volume = 3 Suppl | pages = 1178–83 | date = November 2000 | pmid = 11127835 | doi = 10.1038/81453 | s2cid = 2048100 }}</ref>
The neuronal circuitry affected by LTP/LTD and modified by scaling and metaplasticity leads to reverberatory neural circuit development and regulation in a Hebbian manner which is manifested as memory, whereas the changes in neural circuitry, which begin at the level of the synapse, are an integral part in the ability of an organism to learn.<ref>
{{cite journal | vauthors = Cooper SJ | title = Donald O. Hebb's synapse and learning rule: a history and commentary | journal = Neuroscience and Biobehavioral Reviews | volume = 28 | issue = 8 | pages = 851–74 | date = January 2005 | pmid = 15642626 | doi = 10.1016/j.neubiorev.2004.09.009 | s2cid = 40805686 }}</ref>

There is also a specificity element of biochemical interactions to create synaptic plasticity, namely the importance of location. Processes occur at microdomains – such as [[exocytosis]] of AMPA receptors is spatially regulated by the [[t-SNARE]] [[STX4]].<ref>{{cite journal | vauthors = Kennedy MJ, Davison IG, Robinson CG, Ehlers MD | title = Syntaxin-4 defines a domain for activity-dependent exocytosis in dendritic spines | journal = Cell | volume = 141 | issue = 3 | pages = 524–35 | date = April 2010 | pmid = 20434989 | pmc = 2874581 | doi = 10.1016/j.cell.2010.02.042 }}</ref> Specificity is also an important aspect of CAMKII signaling involving nanodomain calcium.<ref name="Seok-Jin09"/>
The spatial gradient of PKA between dendritic spines and shafts is also important for the strength and regulation of synaptic plasticity.<ref name="Haining09"/> It is important to remember that the biochemical mechanisms altering synaptic plasticity occur at the level of individual synapses of a neuron. Since the biochemical mechanisms are confined to these "microdomains," the resulting synaptic plasticity affects only the specific synapse at which it took place.

==Theoretical mechanisms==
A bidirectional model, describing both LTP and LTD, of synaptic plasticity has proved necessary for a number of different learning mechanisms in [[computational neuroscience]], [[neural networks (biology)|neural networks]], and [[biophysics]]. Three major hypotheses for the molecular nature of this plasticity have been well-studied, and none are required to be the exclusive mechanism:
# Change in the probability of glutamate release.
# Insertion or removal of post-synaptic AMPA receptors.
# [[Phosphorylation]] and de-phosphorylation inducing a change in AMPA receptor conductance.

Of these, the latter two hypotheses have been recently mathematically examined to have identical calcium-dependent dynamics which provides strong theoretical evidence for a calcium-based model of plasticity, which in a linear model where the total number of receptors are conserved looks like

:<math>\frac{d W_i(t)}{d t}=\frac{1}{\tau([Ca^{2+}]_i)}\left(\Omega([Ca^{2+}]_i)-W_i\right),</math>

where

* <math>W_i</math> is the [[synaptic weight]] of the <math>i</math>th input axon,
* <math>[Ca^{2+}]</math> is the concentration of calcium,
* <math>\tau</math> is a time constant dependent on the insertion and removal rates of neurotransmitter receptors, which is dependent on <math>[Ca^{2+}]</math>, and
* <math>\Omega=\beta A_m^{\rm fp}</math> is also a function of the concentration of calcium that depends linearly on the number of receptors on the membrane of the neuron at some fixed point.

Both <math>\Omega</math> and <math>\tau</math> are found experimentally and agree on results from both hypotheses. The model makes important simplifications that make it unsuited for actual experimental predictions, but provides a significant basis for the hypothesis of a calcium-based synaptic plasticity dependence.<ref>{{cite journal | vauthors = Shouval HZ, Castellani GC, Blais BS, Yeung LC, Cooper LN | title = Converging evidence for a simplified biophysical model of synaptic plasticity | journal = Biological Cybernetics | volume = 87 | issue = 5–6 | pages = 383–91 | date = December 2002 | pmid = 12461628 | doi = 10.1007/s00422-002-0362-x | s2cid = 7753630 | url = http://physics.brown.edu/physics/researchpages/Ibns/Lab%20Publications%20(PDF)/converging.pdf | author5-link = Leon Cooper }}</ref>

==Short-term plasticity==
Short-term synaptic plasticity acts on a timescale of tens of milliseconds to a few minutes unlike long-term plasticity, which lasts from minutes to hours. Short-term plasticity can either strengthen or weaken a synapse.

===Synaptic enhancement===
Short-term synaptic enhancement results from an increased probability of synaptic terminals releasing transmitters in response to pre-synaptic action potentials. Synapses will strengthen for a short time because of an increase in the amount of packaged transmitter released in response to each action potential.<ref>{{cite journal | vauthors = Stevens CF, Wesseling JF | title = Augmentation is a potentiation of the exocytotic process | journal = Neuron | volume = 22 | issue = 1 | pages = 139–46 | date = January 1999 | pmid = 10027296 | doi = 10.1016/S0896-6273(00)80685-6 | doi-access = free }}</ref> Depending on the time scales over which it acts synaptic enhancement is classified as [[neural facilitation]], [[synaptic augmentation]] or [[post-tetanic potentiation]].

===Synaptic depression===
[[Synaptic fatigue]] or depression is usually attributed to the depletion of the readily releasable vesicles. Depression can also arise from post-synaptic processes and from feedback activation of presynaptic receptors.<ref>{{cite journal | vauthors = Zucker RS, Regehr WG | title = Short-term synaptic plasticity | journal = Annual Review of Physiology | volume = 64 | pages = 355–405 | date = Mar 2002 | pmid = 11826273 | doi = 10.1146/annurev.physiol.64.092501.114547 | s2cid = 7980969 }}</ref>
[[Heterosynaptic plasticity|heterosynaptic]] depression is thought to be linked to the release of [[adenosine triphosphate]] (ATP) from [[astrocyte]]s.<ref name="Glia">{{cite journal | vauthors = Ben Achour S, Pascual O | title = Glia: the many ways to modulate synaptic plasticity | journal = Neurochemistry International | volume = 57 | issue = 4 | pages = 440–5 | date = November 2010 | pmid = 20193723 | doi = 10.1016/j.neuint.2010.02.013 | s2cid = 1718772 }}</ref>

==Long-term plasticity==
[[Long-term depression]] (LTD) and [[long-term potentiation]] (LTP) are two forms of long-term plasticity, lasting minutes or more, that occur at excitatory synapses.<ref name="NewT"/> NMDA-dependent LTD and LTP have been extensively researched, and are found to require the binding of [[glutamate]], and [[glycine]] or [[D-serine]] for activation of NMDA receptors.<ref name="Glia"/>
The turning point for the synaptic modification of a synapse has been found to be modifiable itself, depending on the history of the synapse.<ref name="pmid7619513">{{cite journal | vauthors = Bear MF | title = Mechanism for a sliding synaptic modification threshold | journal = Neuron | volume = 15 | issue = 1 | pages = 1–4 | date = July 1995 | pmid = 7619513 | doi = 10.1016/0896-6273(95)90056-x | doi-access = free }}</ref> Recently, a number of attempts have been made to offer a comprehensive model that could account for most forms of synaptic plasticity.<ref name="pmid21348800">{{cite journal | vauthors = Michmizos D, Koutsouraki E, Asprodini E, Baloyannis S | title = Synaptic plasticity: a unifying model to address some persisting questions | journal = The International Journal of Neuroscience | volume = 121 | issue = 6 | pages = 289–304 | date = June 2011 | pmid = 21348800 | doi = 10.3109/00207454.2011.556283 | s2cid = 24610392 }}</ref>

===Long-term depression===
Brief activation of an excitatory pathway can produce what is known as long-term depression (LTD) of synaptic transmission in many areas of the brain. LTD is induced by a minimum level of postsynaptic depolarization and simultaneous increase in the intracellular calcium concentration at the postsynaptic neuron. LTD can be initiated at inactive synapses if the calcium concentration is raised to the minimum required level by heterosynaptic activation, or if the extracellular concentration is raised. These alternative conditions capable of causing LTD differ from the Hebb rule, and instead depend on synaptic activity modifications. [[D-serine]] release by [[astrocyte]]s has been found to lead to a significant reduction of LTD in the hippocampus.<ref name="Glia"/>
Activity-dependent LTD was investigated in 2011 for the electrical synapses (modification of Gap Junctions efficacy through their activity).<ref name="pmid22021860">{{cite journal | vauthors = Haas JS, Zavala B, Landisman CE | title = Activity-dependent long-term depression of electrical synapses | journal = Science | volume = 334 | issue = 6054 | pages = 389–93 | date = October 2011 | pmid = 22021860 | doi = 10.1126/science.1207502 | bibcode = 2011Sci...334..389H | s2cid = 35398480 | pmc = 10921920 }}</ref> In the brain, cerebellum is one of the structures where LTD is a form of neuroplasticity.<ref>{{cite journal | vauthors = Mitoma H, Kakei S, Yamaguchi K, Manto M | title = Physiology of Cerebellar Reserve: Redundancy and Plasticity of a Modular Machine | journal = Int. J. Mol. Sci. | volume = 22 | pages = 4777 |  date = April 2021 | issue = 9 | doi = 10.3390/ijms22094777 | pmid = 33946358 | pmc = 8124536 | doi-access = free }}</ref>

===Long-term potentiation===
Long-term potentiation, commonly referred to as LTP, is an increase in synaptic response following potentiating pulses of electrical stimuli that sustains at a level above the baseline response for hours or longer. LTP involves interactions between postsynaptic neurons and the specific presynaptic inputs that form a synaptic association, and is specific to the stimulated pathway of synaptic transmission. 
The long-term stabilization of synaptic changes is determined by a parallel increase of pre- and postsynaptic structures such as [[Bouton (synapse)|axonal bouton]], [[dendritic spine]] and [[postsynaptic density]].<ref name="stabilization_plasticity" />
On the molecular level, an increase of the postsynaptic scaffolding proteins [[PSD-95]] and [[HOMER1|Homer1c]] has been shown to correlate with the stabilization of synaptic enlargement.<ref name="stabilization_plasticity" />

Modification of astrocyte coverage at the synapses in the hippocampus has been found to result from the [[LTP induction|induction of LTP]], which has been found to be linked to the release of [[D-serine]], [[nitric oxide]], and the [[chemokine]], [[s100B]] by [[astrocyte]]s.<ref name="Glia"/>
LTP is also a model for studying the synaptic basis of Hebbian plasticity. Induction conditions resemble those described for the initiation of long-term depression (LTD), but a stronger depolarization and a greater increase of calcium are necessary to achieve LTP.<ref>
{{cite journal | vauthors = Artola A, Singer W | title = Long-term depression of excitatory synaptic transmission and its relationship to long-term potentiation | journal = Trends in Neurosciences | volume = 16 | issue = 11 | pages = 480–7 | date = November 1993 | pmid = 7507622 | doi = 10.1016/0166-2236(93)90081-V | s2cid = 3974242 }}</ref> Experiments performed by stimulating an array of individual dendritic spines, have shown that synaptic cooperativity by as few as two adjacent dendritic spines prevents LTD, allowing only LTP.<ref>{{cite journal|vauthors=Tazerart S, Mitchell DE, Miranda-Rottmann S, Araya R|date=August 2020|title=A spike-timing-dependent plasticity rule for dendritic spines|journal=Nature Communications|volume=11|issue=1|pages=4276|doi=10.1038/s41467-020-17861-7|pmc=7449969|pmid=32848151|bibcode=2020NatCo..11.4276T}}</ref>

==Synaptic strength==
The modification of [[synaptic strength]] is referred to as functional plasticity. Changes in synaptic strength involve distinct mechanisms of particular types of [[glial cell]]s, the most researched type being [[astrocyte]]s.<ref name="Glia"/>

==Computational use of plasticity==
Every kind of synaptic plasticity has different computational uses.<ref>{{cite journal | vauthors = Prati E | title = Atomic scale nanoelectronics for quantum neuromorphic devices: comparing different materials | journal =  International Journal of Nanotechnology | volume = 13 | issue = 7 | pages = 509–523 | year = 2016 | doi = 10.1504/IJNT.2016.078543| arxiv = 1606.01884 | bibcode = 2016IJNT...13..509P | s2cid = 18697109 }}</ref>
Short-term facilitation has been demonstrated to serve as both working memory and mapping input for readout, short-term depression for removing auto-correlation. Long-term potentiation is used for spatial memory storage while long-term depression for both encoding space features, selective weakening of synapses and clearing old memory traces respectively. Forward [[spike-timing-dependent plasticity]] is used for long range temporal correlation, temporal coding and spatiotemporal coding. The reversed [[spike-timing-dependent plasticity]] acts as sensory filtering.

== See also ==
{{col div|colwidth=30em}}
* [[Homosynaptic plasticity]]
* [[Homeostatic plasticity]]
* [[Inhibitory postsynaptic potential]]
* [[Activity-dependent plasticity]]
* [[Neural backpropagation]]
* [[Neuroplasticity]]
* [[Postsynaptic potential]]
* [[Non-synaptic plasticity]]
{{colend}}

== References ==
{{Reflist|colwidth=35em}}

== Further reading ==
{{refbegin}}
* {{cite journal| vauthors = Thornton JK |year=2003|title=New LSD Research: Gene Expression within the Mammalian Brain |url=http://www.maps.org/news-letters/v13n1/13124tho.html|journal=MAPS|volume=13|issue=1|access-date=2007-06-08}}
* {{cite journal | vauthors = Chapouthier G | author-link1 = Georges Chapouthier | title = From the search for a molecular code of memory to the role of neurotransmitters: a historical perspective | journal = Neural Plasticity | volume = 11 | issue = 3–4 | pages = 151–8 | date = 2004 | pmid = 15656266 | pmc = 2567045 | doi = 10.1155/NP.2004.151 | doi-access = free }}
* {{cite journal | vauthors = Hawkins RD, Kandel ER, Bailey CH | title = Molecular mechanisms of memory storage in Aplysia | journal = The Biological Bulletin | volume = 210 | issue = 3 | pages = 174–91 | date = June 2006 | pmid = 16801493 | doi = 10.2307/4134556 | jstor = 4134556 | s2cid = 16448344 }}
* {{cite book | author-link1 = Joseph E. LeDoux | vauthors = LeDoux J | title = Synaptic Self: How Our Brains Become Who We Are. | location = New York | publisher = Penguin Books | date = 2002 | pages = 1–324 }}
{{refend}}

== External links ==
* [http://icwww.epfl.ch/~gerstner//SPNM/node71.html Overview] {{Webarchive|url=https://web.archive.org/web/20170502074457/http://icwww.epfl.ch/~gerstner/SPNM/node71.html |date=2017-05-02 }}
* [https://web.archive.org/web/20090210041801/http://cnr.iop.kcl.ac.uk/default.aspx?pageid=169 Finnerty lab, MRC Centre for Neurodegeneration Research, London]
*[https://web.archive.org/web/20100119002009/http://www.bris.ac.uk/synaptic/public/plasticity.htm Brain Basics Synaptic Plasticity Synaptic transmission is plastic]
* [http://nba.uth.tmc.edu/neuroscience/s1/chapter07.html Synaptic Plasticity], ''Neuroscience Online'' (electronic neuroscience textbook by UT Houston Medical School)

=== Videos, podcasts ===
* [http://videocast.nih.gov/Summary.asp?file=13746 Synaptic plasticity: Multiple mechanisms and functions] - a lecture by Robert Malenka, M.D., Ph.D., [[Stanford University]]. Video podcast, runtime: 01:05:17.

{{Nervous system physiology}}

{{DEFAULTSORT:Synaptic Plasticity}}
[[Category:Neuroscience of memory]]
[[Category:Neuroplasticity]]
[[Category:Neurology]]
[[Category:Neural synapse]]
[[Category:Neural circuitry]]

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