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Main article: Neural plasticity

Metaplasticity is a term originally coined by W.C. Abraham and M.F. Bear to refer to the plasticity of synaptic plasticity. Until that time synaptic plasticity had referred to the plastic nature of individual synapses. However this new form referred to the plasticity of the plasticity itself, thus the term meta-plasticity. The idea is that the synapse's previous history of activity determines its current plasticity. This may play a role in some of the underlying mechanisms thought to be important in memory and learning such as Long-term potentiation (LTP), Long-term Depression (LTD) and so forth. These mechanisms depend on current synaptic "state", as set by ongoing extrinsic influences such as the level of synaptic inhibition, the activity of modulatory afferents such as catecholamines, and the pool of hormones affecting the synapses under study. Recently, it has become clear that the prior history of synaptic activity is an additional variable that influences the synaptic state, and thereby the degree, of LTP or LTD produced by a given experimental protocol. In a sense, then, synaptic plasticity is governed by an activity-dependent plasticity of the synaptic state; such plasticity of synaptic plasticity has been termed metaplasticity. There is little known about metaplasticity, and there is much research currently underway on the subject, despite its difficulty of study, because of its theoretical importance in brain and cognitive science. Most research of this type is done via cultured hippocampus cells or hippocampal slices.

Historical discoveries

Hebbian Plasticity

The brain is “plastic”, meaning it can be moulded and formed. This plasticity is what allows you to learn throughout your lifetime (Thiagarajan et al. 2007, p. 156); your synapses change based on your experience. New synapses can be made, old ones destroyed, or existing ones can be strengthened or weakened. The original theory of plasticity is called “Hebbian plasticity”, named after Donald Hebb in 1949. A quick but effective summary of Hebbian theory is that “cells that fire together, wire together”, together being the key word here which will be explained shortly. Hebb described an early concept of the theory, not the actual mechanics themselves. Hebbian plasticity involves two mechanisms: LTP and LTD, discovered by Bliss and Lomo in 1973. LTP, or long-term potentiation, is the increase of synapse sensitivity due to a prolonged period of activity in both the presynaptic and postsynaptic neuron. This prolonged period of activity is normally concentrated electric impulses, usually around 100 Hz. It is called “coincidence” detection in that it only strengthens the synapse if there was sufficient activity in both the presynaptic and postsynaptic cells. If the postsynaptic cell does not become sufficiently depolarized then there is no coincidence detection and LTP/LTD do not occur. LTD, or long-term depression, works the same way however it focuses on a lack of depolarization coincidence. LTD can be induced by electrical impulses at around 5 Hz. These changes are synapse specific. A neuron can have many different synapses all controlled via the same mechanisms defined here.

The earliest proposed mechanism for plastic activity is based around glutamate receptors and their ability to change in number and strength based on synapse activity. Glutamate has two main receptor types: AMPA and NMDA. These are named after drugs that bind to the receptors (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate, respectively) however they all bind glutamate. When a glutamatergic synapse releases glutamate it binds to both the AMPA and the NMDA receptors. The AMPA receptors are ionotropic receptors that are responsible for fast synaptic transmission. In a nutshell the NMDA receptors evoke a response in the cell only when sufficient glutamate has been transmitted to cause that cell to depolarize enough to unblock the NMDA receptor. Sufficient depolarization in the membrane will cause the magnesium cation blockade in the NMDA receptors to vacate, thus allowing calcium influx into the cell. NMDA receptors are "coincidence" detectors. They determine when the presynaptic and postsynaptic neuron are linked in time via activity. When this occurs, NMDA receptors become the control mechanism that dictates how the AMPA and NMDA receptors are to be rearranged. The rearrangement of AMPA and NMDA receptors has become the central focus of current studies of metaplasticity as it directly determines LTP and LTD thresholds. There is large amounts of research focused on finding the specific enzymes and intracellular pathways involved in the NMDAR-mediated modulation of membrane AMPA receptors. Recent biochemical research has shown that a deficiency in the protein tenascin-R (TNR) leads to a metaplastic increase in the threshold for LTP induction. TNR is an extracellular-matrix protein expressed by oligodendrocytes during myelination (Bukalo, Schachner & Dityatev 2007, p. 6019).

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 hippocampi of anaesthetised rabbits. They were able to show a burst of tetanic (100 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 dendate 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.

Synaptic States

Research in 2004 has shown that synapses do not strengthen or weaken on a sliding scale. There are discrete states that synapses move between. These states are active, silent, recently-silent, potentiated, and depressed. The states which they can move to are dependent on the state that they are in at the moment. Thus, the future state is determined by the state gained by previous activity. For instance, silent (but not recently-silent) synapses can be converted to active via the insertion of AMPARs in the postsynaptic membrane. Active synapses can move to either potentiated or depressed via LTP or LTD respectively. Prolonged low-frequency stimulation (5 Hz, the method used to induce LTD) can move an active synapse to depressed and then silent. However, synapses that have just become active cannot be depressed or silenced. Thus there is state-machine-like behavior at the synapse when it comes to transitions. However, the states themselves can have varying degrees of intensity. One active-state synapse can be stronger than another active-state synapse. This is, in theory, how you can have a strong memory vs. a weak memory. The strong memories are the ones with very heavily populated active synapses, while weak memories may still be active but poorly populated with AMPARs. The same research has shown that NMDA receptors themselves, once thought to be the control mechanism behind AMPA receptor organization, can be regulated by synaptic activity (Montgomery & Madison 2004, p. 744). This regulation of the regulation mechanism itself adds another layer of complexity to the biology of the brain.

Biochemical mechanisms

Two molecular mechanisms for synaptic plasticity (researched by the Eric Kandel laboratories) 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 Ca2+ 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 Mg2+ ions, resulting in less Ca2+ entering the post-synaptic neuron and lower intracellular Ca2+ concentrations (which activate protein phosphatases and induce long-term depression, LTD).[1]

These activated protein kinases serve to phosphorylate post-synaptic excitatory receptors (e.g. AMPA receptors), improving cation conduction, and thereby potentiating the synapse. Also, this signals recruitment of additional receptors into the post-synaptic membrane, and stimulates 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.[2]

The second mechanism depends on a second messenger cascade regulating gene transcription and changes in the levels of key proteins at synapses 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.[3] 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.[4] 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 messengers. Phosphodiesterase, for example, breaks down the secondary messenger cAMP, which has been implicated in increased AMPA receptor synthesis in the post-synaptic neuron [citation needed].

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 MAP kinase pathway. By changing the F-actin cytoskeletal structure of dendritic spines, spines are lengthened and the chance that they make synaptic contacts with the axonal terminals of the presynaptic cell is increased. The end result is long term maintenance of LTP.[5]

The number of ion channels on the post-synaptic membrane affects the strength of the synapse.[6] 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, N-methyl D-aspartate receptor (NMDA receptor) and AMPA receptors are added to the membrane by exocytosis and removed by endocytosis.[7][8][9] These processes, and by extension the number of receptors on the membrane, can be altered by synaptic activity.[7][9] 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.[10] 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. 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.[9] Synaptic scaling is a primary mechanism by which a neuron is able to stabilize firing rates up or down.[11]

Synaptic scaling serves to maintain the strengths of synapses relative to each other, lowering amplitudes of small excitatory postsynaptic potentials in response to continual excitation and raising them after prolonged blockage or inhibition.[9] This effect occurs gradually over hours or days, by changing the numbers of NMDA receptors 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 Ca2+ 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.[12] Synaptic scaling is a primary mechanism by which a neuron to be selective to its varying inputs.[13] 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.[14]

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.[15] Specificity is also an important aspect of CAMKII signaling involving nanodomain calcium.[16] The spatial gradient of PKA between dendritic spines and shafts is also important for the strength and regulation of synaptic plasticity.[3] 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, 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:

  1. Change in the probability of glutamate release.
  2. Insertion or removal of post-synaptic AMPA receptors.
  3. Phosphorylation and de-phosphorylation inducing a change in AMPA receptor conductance.

Of these, the first 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

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

where W_i is the synaptic weight of the ith input axon, \tau is a time constant dependent on the insertion and removal rates of neurotransmitter receptors, which is dependent on [Ca^{2+}], the concentration of calcium. \Omega=\beta A_m^{\rm fp} 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 \Omega and \tau 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.[17]

Short-term plasticity

Plasticity can be categorized as short-term, lasting a few seconds or less, or long-term, which lasts from minutes to hours. Short-term synaptic enhancement results from an increase in the probability that synaptic terminals will release transmitters in response to pre-synaptic action potentials. Synapses will strengthen for a short time because of either an increase in size of the readily releasable pool of packaged transmitter or an increase in the amount of packaged transmitter released in response to each action potential.[18] Types of short term plasticity include synaptic augmentation, depression, facilitation, or neural facilitation, and post-tetanic potentiation.

Synaptic augmentation

Synaptic augmentation is the increased efficacy of synapse lasting in the order of seconds (7 s often quoted). It has been found to be associated with increased efficiency with which action potentials cause release of vesicles containing transmitters.

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.[19] Heterosynaptic depression is thought to be linked to the release of adenosine triphosphate (ATP) from astrocytes.[20]

Long-term plasticity

Long-term depression and long-term potentiation are two forms of long-term plasticity, lasting minutes or more, that occur at excitatory synapses.[21] 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.[20]

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 astrocytes has been found to lead to a significant reduction of LTD in the hippocampus.[20] A LTD was evidenced in 2011 for the electrical synapses (modification of Gap Junctions efficacy through their activity).[22]

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. Modification of astrocyte coverage at the synapses in the hippocampus has been found to result from the induction of LTP, which has been found to be linked to the release of D-serine, nitric oxide, and the chemokine, s100B by astrocytes.[20] 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.[23]

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 cells, the most researched type being astrocytes.[20]

Synaptic Tagging

Recent research (Young et al. 2006, p. 1784) has found a mechanism known as "synaptic tagging". When new receptor proteins are being expressed and synthesized they must also be transported to the synaptic membrane, and some sort of chemical messaging is required for this. Their research has shown that activation of cAMP/PKA signaling pathways is required for LTP induction due to its "tagging" nature. It was even shown that simple pharmacological activation of cAMP/PKA pathways was sufficient for the synapse to be tagged, completely independent of any sort of activity.

NMDA Receptors

The NMDA receptor is made up of three subunits: NR1, a variable NR2 subunit, and a variable NR3 subunit. Two NR2 subunits in particular have been the subject of intense study: NR2A and NR2B. The NR2B subunit not only is more sensitive to glutamate and takes longer to desensitize, but also allows more calcium entrance into the cell when it opens. A low NR2A/NR2B ratio is generally correlated with a decreased threshold of activation caused by rearing animals in light-deprived environments. This has been shown experimentally via light deprivation studies in which it was shown that the NR2A/B ratio declined. The threshold can be increased in some situations via light exposure. Studies of this nature were used to find the critical period for formation of the visual system in cats. This shifting ratio is a measurement of LTD/LTP threshold and thus has been posited as a metaplasticity mechanism (Philpot, Cho & Bear 2007, p. 495).


Glial cells not only provide structural and nutritional support for neurons, but also provide processing support via chemicals known as gliotransmitters. Gliotransmitters include glutamate, ATP, and, more recently, the amino acid D-serine. Once thought to be glycine itself, D-serine serves as a ligand in the glycine site of NMDARs. D-serine is synthesized by astrocytes and is heavily co-localized with NMDARs. Without D-serine there can be no NMDA-induced neurotoxicity, or almost any NMDA response of any kind. Due to this evidence it is clear that D-serine is an essential ligand for the NMDA receptors. An essential factor in this research is the fact that astrocytes will vary their coverage of neurons based on the physiological processes of the body. Oxytocin and vasopressin neurons will have more NMDA receptors exposed due to astrocyte activity during lactation than during normal functioning. This research took place mostly in cells from the hypothalamic supraoptic nucleus, or SON. Due to synaptic plasticity being almost completely dependent on NMDAR processing, dynamic astrocyte NMDAR coverage is by nature a metaplasticity parameter (Panatier 2006, p. 775).

Synaptic Homeostasis

Homeostatic plasticity manages synaptic connections across the entire cell in an attempt to keep them at manageable connection levels. Hebbian methods tend to drive networks into either a maximized state or a minimized state of firing, thus limiting the potential activity and growth of the network. With homeostatic mechanisms in place there is now a sort of "gain control" which allows these Hebbian methods to be checked in order to maintain their information processing abilities (Thiagarajan et al. 2007, p. 156). This kind of modulation is important to combat intense lack of neural activity, such as prolonged sensory deprivation (in this study in particular it is light-deprivation affecting visual cortex neurons) or damage caused by stroke. Synaptic scaling is a mechanism in place to hold synapse sensitivity at normalized levels. Prolonged periods of inactivity increase the sensitivity of the synapses so that their overall activity level can remain useful. Chronic activity causes desensitization of the receptors, lowering overall activity to a more biologically manageable level. Both AMPA and NMDA receptor levels are affected by this process and so the overall “weight” of each synaptic connection (refined by Hebbian methods) is maintained while still increasing the overall level of activity over the entire neuron. It has been shown that both the presynaptic and the postsynaptic neuron are involved in the process, changing the vesicle turnover rate and AMPA receptor composition respectively (Perez-Ontano & Ehlers 2005).

Recent research has found that the calcium-dependent enzyme CaMKII, which exists in an alpha and beta isoform, is key in inactivity-dependent modulation. A low alpha/beta ratio causes an increased threshold for cellular excitation via calcium influx and thus favors LTP (Thiagarajan et al. 2007, p. 156).

Endocannabinoid Metaplasticity

Research in 2004 has shown that endocannabinoid release from the postsynaptic neuron can inhibit activation of the presynaptic neuron. Type 1 canabbinioid receptors (CB1Rs) are the receptors on the presynaptic neuron responsible for this effect. The specific ligand is thought to be 2-arachidonyl glycerol, or 2-AG. This has mainly been found in GABAergic synapses and thus has been termed inihibitory long term depression (I-LTD). This effect has been found to be extremely localized and accurate, meaning the cannabinoids do not diffuse far from their intended target. This inhibition primes the synapses for future LTP induction and is thus metaplastic in nature (Chevaleyre & Castillo 2004, p. 871).

Neuronal adaptation mechanism

A new mechanism has been proposed that concerns the innate excitability of a neuron. It is quantified by the size of the hyperpolarization in mV due to K+ channels re-opening during an action potential. After any sort of learning task, particularly a classical or operant conditioning task, the amplitude of the K+ hyperpolarization, or "after hyperpolarization (AHP)", is greatly reduced. Over time this AHP will return to normal levels. This normalization does not correlate with a loss of memory but instead a loss of learning potential. (Zelcer et al. Grossberger, p. 460)

See also


  1. Bear MF, Connors BW, and Paradisio MA. 2007. Neuroscience: Exploring the Brain, 3rd ed. Lippincott, Williams & Wilkins
  2. (2000). Postsynaptic protein phosphorylation and LTP. Trends in Neurosciences 23 (2): 75–80.
  3. 3.0 3.1 Haining, Z., Sia G., Sato T., Gray N., Mao T., Khuchia Z., Huganir R., Svodoba K. (2009). Subcellular Dynamics of Type II PKA in Neurons. Cell Press 62: 363–374.
  4. Seok-Jin, R., Escobedo-Lozoya Y., Szatmari E., Yasuda R. (2009). Activation of CaMKII in single dendritic spines during long-term potentiation. Nature 458 (19): 299–306.
  5. Shoji-Kasai, Yoko, Hiroshi Ageta, Yoshihisa Hasegawa, Kunihiro Tsuchida, Hiromu Sugino, Kaoru Inokuchi (2007). Activin increases the number of synaptic contacts and the length of dendritic spine necks by modulating spinal actin dynamics. Journal of Cell Science 120 (Pt 21): 3830–3837.
  6. Debanne, D., Daoudal G., Sourdet V., and Russier M. (2003). Brain plasticity and ion channels. Journal of Physiology, Paris 97 (4-6): 403–414.
  7. 7.0 7.1 Shi, S.H., Hayashi Y., Petralia R.S., Zaman S.H., Wenthold R., Svoboda K., Malinow R. (1999). Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation. Science 284 (5421): 1811–1816.
  8. Song, I., Huganir R.L. (2002). Regulation of AMPA receptors during synaptic plasticity. Trends in Neurosciences 25 (11): 578–589.
  9. 9.0 9.1 9.2 9.3 Pérez-Otaño, I., Ehlers M.D. (2005). Homeostatic plasticity and NMDA receptor trafficking. Trends in Neurosciences 28 (5): 229–238. [dead link]
  10. Bear, M.F. (2007). Neuroscience: Exploring the Brain, 779, Lippincott Williams & Wilkins.
  11. Desai, Niraj S., Robert H. Cudmore, Sacha B. Nelson & Gina G. Turrigiano (2002). Critical periods for experience-dependent synaptic scaling in visual cortex. Nature Neuroscience 5 (8): 783–789.
  12. Abraham, Wickliffe, Warren P. Tate (1997). Metaplasticity: A new vista across the field of synaptic plasticity. Progress in Neurobiology 52 (4): 303–323.
  13. Abbott, L., Sacha B. Nelson (2000). Synaptic plasticity: taming the beast. Nature Neuroscience 3: 1178–1183.
  14. Cooper, Stephen J. (2005). Donald O. Hebb's synapse and learning rule: a history and commentary. Neuroscience and Biobehavioral Reviews 28 (8): 851–874.
  15. Kennedy, Matthew J., Ian G. Davison, Camenzind G. Robinson, and Michael D. Ehlers (2010). Syntaxin-4 Defines a Domain for Activity-Dependent Exocytosis in Dendritic Spines. Cell 141 (3): 1–12.
  16. Lee, Seok-Jin R., Yasmin Escobedo-Lozoya, Erzsebet M. Szatmari, and Ryohei Yasuda (2009). Activation of CaMKII in single dendritic spines during long-term potentiation. Nature 458 (7236): 299–304.
  17. Shouval, Harel Z., Gastone C. Castellani, Brian S. Blais, Luk C. Yeung, Leon N. Cooper (2002). Converging evidence for a simplified biophysical model of synaptic plasticity. Biological Cybernetics 87 (5-6): 383–391.
  18. Stephens, Charles S. (Jan 1999). Augmentation Is a Potentiation of the Exocytotic Process. Neuron 22 (1): 139–146.
  19. Zucker, Robert S. (Mar 2002). Short-term Synaptic Plasticity. Annual Review of Physiology 64: 355–405.
  20. 20.0 20.1 20.2 20.3 20.4 Achour, S. Ben (Mar 2010). Glia: The many ways to modulate synaptic plasticity. Neurochemistry International 57 (4): 440–445.
  21. Cite error: Invalid <ref> tag; no text was provided for refs named NewT
  22. J. S. Haas, B. Zavala, C. E. Landisman, Activity-dependent long-term depression of electrical synapses. Science 334, 389–393 (2011). [Abstract] [Full Text]
  23. Artola, Alain (1993). Long-term depression of excitatory synaptic transmission and its relationship to long-term potentiation. Trends in Neuroscience 16 (11): 480–487.
  • Zelcer I, Cohen H, Richter-Levin G, Lebiosn T, Grossberger T, Barkai E (April 2006). A cellular correlate of learning-induced metaplasticity in the hippocampus. Cereb. Cortex 16 (4): 460–8..
  • Abraham WC, Bear MF (April 1996). Metaplasticity: the plasticity of synaptic plasticity. Trends Neurosci. 19 (4): 126–30..
  • Montgomery JM, Madison DV (December 2004). Discrete synaptic states define a major mechanism of synapse plasticity. Trends Neurosci. 27 (12): 744–50..
  • Pérez-Otaño I, Ehlers MD (May 2005). Homeostatic plasticity and NMDA receptor trafficking. Trends Neurosci. 28 (5): 229–38..
  • Chevaleyre V, Castillo PE (September 2004). Endocannabinoid-mediated metaplasticity in the hippocampus. Neuron 43 (6): 871–81..
  • Philpot BD, Cho KK, Bear MF (February 2007). Obligatory role of NR2A for metaplasticity in visual cortex. Neuron 53 (4): 495–502..
  • Thiagarajan TC, Lindskog M, Malgaroli A, Tsien RW (January 2007). LTP and adaptation to inactivity: overlapping mechanisms and implications for metaplasticity. Neuropharmacology 52 (1): 156–75..
  • Young JZ, Isiegas C, Abel T, Nguyen PV (April 2006). Metaplasticity of the late-phase of long-term potentiation: a critical role for protein kinase A in synaptic tagging. Eur. J. Neurosci. 23 (7): 1784–94..
  • Bukalo O, Schachner M, Dityatev A (May 2007). Hippocampal metaplasticity induced by deficiency in the extracellular matrix glycoprotein tenascin-R. J. Neurosci. 27 (22): 6019–28..
  • MacDonald JF, Jackson MF, Beazely MA (April 2007). G protein-coupled receptors control NMDARs and metaplasticity in the hippocampus. Biochim. Biophys. Acta 1768 (4): 941–51..
  • Panatier A, Theodosis DT, Mothet JP, et al. (May 2006). Glia-derived D-serine controls NMDA receptor activity and synaptic memory. Cell 125 (4): 775–84..

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