Metaplasticity: the plasticity of synaptic plasticity
Trends in NeurosciencesPublished 1 April 1996
Wickliffe C. Abraham, Mark F. Bear
Citations1,766
SJR quartileQ1
SJR score4.73
SNIP3.68
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
Experimental evidence for a novel form of persistent synaptic plasticity called metaplasticity is reviewed, which might involve alterations in NMDA-receptor function in some cases, but there are many other candidate mechanisms.
Abstract
In this paper, we review experimental evidence for a novel form of persistent synaptic plasticity we call metaplasticity. Metaplasticity is induced by synaptic or cellular activity, but it is not necessarily expressed as a change in the efficacy of normal synaptic transmission. Instead, it is manifest as a change in the ability to induce subsequent synaptic plasticity, such as long-term potentiation or depression. Thus, metaplasticity is a higher-order form of synaptic plasticity. Metaplasticity might involve alterations in NMDA-receptor function in some cases, but there are many other candidate mechanisms. The induction of metaplasticity complicates the interpretation of many commonly studied aspects of synaptic plasticity, such as saturation and biochemical correlates.
Keywords
MedicineNeuroscience
Current Opinion in NeurobiologySynaptic plasticity: LTP and LTD
1,344 Citations1994Mark F. Bear, Robert C. Malenka
A new form of synaptic plasticity, homosynaptic long-term depression (LTD) has also recently been documented, which, like LTP, requires Ca2+ entry through the NMDA receptor, and current work suggests that this LTD is a reversal ofLTP, and that the mechanisms of LTP and LTD may converge at the level of specific phosphoproteins.
CellRegulation of brain Type II Ca2+/calmodulin-dependent protein kinase by autophosphorylation: A Ca2+-triggered molecular switch
861 Citations1986Stephen G. Miller
Changes in enzymatic activity of a prominent brain calmodulin-dependent protein kinase suggest a mechanism by which the kinase could act as a calcium-triggered molecular switch and further prolong the active state by opposing dephosphorylation by cellular phosphatases.
NatureGABAB autoreceptors regulate the induction of LTP
609 Citations1991Ceri H. Davies, Sarah J. Starkey +2 more
It is reported that during high-frequency transmission GABA depresses its own release by an action on GABAB autoreceptors, which permits sufficient NMDA receptor activation for the induction of LTP, and demonstrates a role for GABAB receptors in synaptic plasticity.
Journal of NeuroscienceBidirectional long-term modification of synaptic effectiveness in the adult and immature hippocampus
591 Citations1993Serena M. Dudek, Mark F. Bear
To address the question of whether depressed synapses can still be potentiated and vice versa, LTP was saturated with repeated high- frequency tetani, and then LTD was induced with low-frequency stimulation (LFS), indicating that the same synapses whose transmission had been depressed by LFS were capable of subsequently supporting potentiation.
CellCaMKII regulates the frequency-response function of hippocampal synapses for the production of both LTD and LTP
529 Citations1995Mark Mayford, Jian Wang +2 more
The regulation of this frequency-response function by Ca(2+)-independent CaMKII activity seems to account for two previously unexplained synaptic phenomena, the relative loss of LTD in adult animals compared with juveniles and the enhanced capability for depression of facilitated synapses.
NeuronDual role of calmodulin in autophosphorylation of multifunctional cam kinase may underlie decoding of calcium signals
508 Citations1994Phyllis I. Hanson, Tobias Meyer +2 more
Simulations show that repetitive Ca2+ pulses at limiting calmodulin lead to the recruitment ofCalmodulin to the holoenzyme, which further stimulates autophosphorylation and trapping, and will potentiate the response of the kinase to sequential Ca2- transients and establish a threshold frequency at which the enzyme becomes highly active.
Trends in NeurosciencesThe CaM kinase II hypothesis for the storage of synaptic memory
506 Citations1994John Lisman
Experiments show that activity of CaM kinase II is increased for long periods of time after induction of long-term potentiation, that enhanced activity mimics long- term potentiated activity, and that enzyme activity is necessary for induction ofLong-Term potentiation.
NatureA molecular switch activated by metabotropic glutamate receptors regulates induction of long-term potentiation
427 Citations1994Zuner A. Bortolotto, Zafar I. Bashir +2 more
The role of mGluRs in the induction of LTP is fundamentally different from that of NMDA receptors and this work shows that the molecular switch is a new feature of LTB which has fundamental consequences for the understanding of synaptic plastic mechanisms.
ScienceThe Influence of Prior Synaptic Activity on the Induction of Long-Term Potentiation
416 Citations1992Yan-You Huang, A. Colino +2 more
The results suggest that the threshold for LTP induction may be continually adjusted according to the recent history of NMDA receptor activation and provide a physiological mechanism by which LTP can be transiently inhibited.
NatureLong-term potentiation of NMDA receptor-mediated synaptic transmission in the hippocampus
373 Citations1991Zafar I. Bashir, Simon Alford +3 more
It is reported that a pharmacologically isolated NMDA receptor-mediated synaptic response can undergo robust, synapse-specific LTP, adding fundamentally to theories of synaptic plasticity because NMDA receptors activation may, in addition to causing increased synaptic efficiency, directly alter the plasticity of synapses.
Brain ResearchReversal of long-term potentiation (depotentiation) induced by tetanus stimulation of the input to CA1 neurons of guinea pig hippocampal slices
355 Citations1991Satoshi Fujii, Kazuo Saito +3 more
Significantly less effectiveness was observed for DPS at higher frequencies, with smaller numbers of pulses, featuring a longer time-lag after tetanus and under APV administration, while when DPS was applied before tetanus, significantly less robust LTP was observed.
Trends in NeurosciencesProtein kinase C modulation of NMDA currents: an important link for LTP induction
346 Citations1992Yehezkel Ben‐Ari, Laurent Aniksztejn +1 more
It is suggested that PKC activity may, in fact, determine the threshold of LTP induction, and enhanced kinase activity may underlie the central role of the NMDA receptor--channel complex in neuronal plasticity.
NeuronPostsynaptic factors control the duration of synaptic enhancement in area CA1 of the hippocampus
325 Citations1991Robert C. Malenka
It is demonstrated that NMDA receptor activation can result in distinct forms of synaptic potentiation and imply that the magnitude of postsynaptic calcium increase is a critical variable controlling the duration of synaptic enhancement.
Life SciencesThe effects of repetitive low frequency stimulation on control and “potentiated” synaptic responses in the hippocampus
316 Citations1980Germán Barrionuevo, Frank Schottler +1 more
Trains of low frequency stimulation (LFS) were administered to the Schaffer collateral-commissural projections to the regio superior of the rat hippocampus before and after the induction of long-term potentiation (LTP).
Brain ResearchStable depression of potentiated synaptic responses in the hippocampus with 1–5 Hz stimulation
299 Citations1990Ursula Stäubli, Gary Lynch
Low-frequency stimulation applied prior to induction of LTP had no lasting effects on evoked responses not did it affect responses to a control stimulating electrode in those cases in which it reversed LTP.
Learning & MemoryLow-frequency stimulation erases LTP through an NMDA receptor-mediated activation of protein phosphatases.
297 Citations1994Thomas J. O’Dell, Eric R. Kandel
In the CA1 region of adult guinea pig hippocampal slices, long trains of theta frequency stimulation produced a small enhancement of basal synaptic transmission but depressed the strength of synaptic transmission at synapses that had recently undergone long-term potentiation (LTP).
NaturePresynaptic release probability influences the locus of long-term potentiation
293 Citations1992Alan U. Larkman, Timo Hannay +2 more
A combination of quantal analysis procedures are used to provide evidence that both pre- and postsynaptic changes can contribute substantially to the maintenance of long-term potentiation in the CA1 region of the hippocampus.
Proceedings of the National Academy of SciencesBiophysical model of a Hebbian synapse.
245 Citations1990Anthony M. Zador, Christof Koch +1 more
A biophysical model of electrical and Ca(2+) dynamics following activation of N-methyl-D-aspartate (NMDA) receptors located on a dendritic spine is presented to explore the computational implications of Hebbian synapses.
ScienceInhibition of Long-Term Potentiation by NMDA-Mediated Nitric Oxide Release
233 Citations1992Yukitoshi Izumi, David B. Clifford +1 more
Results indicate that the timing of NO release relative to high-frequency activation of CA1 synapses may be an important determinant of LTP generation and suggest that NO may play a positive or negative modulatory role in LTP depending on prior events at the tetanized synapse and the ambient concentration of excitatory amino acids.
Journal of NeuroscienceGABAergic and developmental influences on homosynaptic LTD and depotentiation in rat hippocampus
230 Citations1995John J. Wagner, BE Alger
The results suggest that the influence of both age and prior synaptic activity on LTD induction can be explained by changes in GABAergic systems in young versus mature, and naive versus tetanized slices.
Experimental Brain ResearchAn investigation of depotentiation of longterm potentiation in the CA1 region of the hippocampus
196 Citations1994Zafar I. Bashir, Graham L. Collingridge
It is shown that prolonged low frequency stimulation can result in an mGluR-dependent depotentiation of LTP, which was reversibly reduced, in a stereoselective manner, by the specific metabotropic glutamate receptor (mGLUR) antagonist.
NeuronSpatial and temporal changes in signal transduction pathways during LTP
183 Citations1994Kerrie L. Thomas, Serge Laroche +3 more
Results show that, during the maintenance phase of LTP in the hippocampus, there are selective increases in the expression of serine/threonine kinases and that these increases have specific and characteristic temporal and spatial profiles.
NeuronPriming of associative long-term depression in the dentate gyrus by θ frequency synaptic activity
180 Citations1992Brian R. Christie, Wickliffe C. Abraham
It is reported here, however, that associative LTD in the lateral path is readily induced after being "primed" by a brief period of lateral path synaptic activity at a theta rhythm frequency (5 Hz).
NatureLong-lasting enhancement of NMDA receptor-mediated synaptic transmission by metabotropic glutamate receptor activation
176 Citations1994John O’Connor, Michael J. Rowan +1 more
It is found that mGlu receptor activation by a selective agonist produced a long-lasting enhancement which was mutually exclusive with long-term potentiation of these NMDA receptor-mediated excitatory postsynaptic currents.
Proceedings of the National Academy of SciencesImmunoreactivity for a calmodulin-dependent protein kinase is selectively increased in macaque striate cortex after monocular deprivation.
167 Citations1986S.H.C. Hendry, Mary B. Kennedy
Findings suggest that either the concentration of type II Ca2+/calmodulin-dependent protein kinase or its accessibility to the antibody probe increases dramatically and selectively in neurons of macaque primary visual cortex that have been deprived of their normal visual input.
NeuronStimulus-induced coordinate changes in mRNA abundance in single postsynaptic hippocampal CA1 neurons
159 Citations1992Scott A. Mackler, Brian P. Brooks +1 more
Changes in mRNA abundance in individual cells, with synaptic and glial interactions intact, combine to produce a molecular fingerprint of a potentiated CA1 neuron.
Neuroscience LettersLow-frequency activation of the NMDA receptor system can prevent the induction of LTP
157 Citations1989E.J. Coan, Andy J. Irving +1 more
It is suggested that certain types of activation of the NMDA receptor system can disable the LTP induction mechanism in rats bathed in Mg2(+)-free medium tetanic stimulation.
Neurochemical ResearchConcerted regulation of protein phosphorylation and dephosphorylation by calmodulin
157 Citations1991Claude B. Klee
A more general scheme is presented here, based on different mechanisms of the calmodulin regulation of the two classes of enzyme, which helps to solve this apparent inconsistency in the mechanism of action of cal modulin.
Journal of NeurophysiologyInsights into associative long-term potentiation from computational models of NMDA receptor-mediated calcium influx and intracellular calcium concentration changes
152 Citations1990William R. Holmes, William B. Levy
The goal was to determine whether Ca2+ influx through NMDA-receptor channels was, by itself, sufficient to explain associative LTP, including control experiments and the temporal requirements of LTP.
Brain ResearchReversal of LTP by theta frequency stimulation
144 Citations1993John Larson, Peng Xiao +1 more
The results suggest that the hippocampal theta rhythm promotes both the induction of LTP and its subsequent reversal with the latter process involving activation of adenosine receptors, and may function to refine or sharpen recently encoded representations.
NeuronIndependent mechanisms for long-term depression of AMPA and NMDA responses
131 Citations1995David K. Selig, Gregory O. Hjelmstad +3 more
By varying the pattern of synaptic stimulation, the responses mediated by one receptor subtype can be modified without affecting the responsesmediated by the other by the mechanisms underlying activity-dependent plasticity of NMDAR-mediated synaptic responses.
Journal of NeurophysiologyIsolated NMDA receptor-mediated synaptic responses express both LTP and LTD
130 Citations1992Xiaping Xie, Thomas Berger +1 more
Hyperpolarization of granule cell membrane potential to -100 mV during 50-Hz tetanic stimuli reversibly blocked the induction of LTP indicating that simultaneous activation of pre- and postsynaptic elements is a prerequisite for potentiation of NMDA receptor-mediated synaptic transmission.
NeuroreportPriming of homosynaptic long-term depression in hippocampus by previous synaptic activity
119 Citations1993Eric Wexler, Patric K. Stanton
To determine whether a 'sliding threshold' of synaptic activity needed to induce long-term depression versus potentiation of synaptic transmission should vary as a function of previous synaptic activity, Schaffer collateral afferents are stimulated in area CA1 of rat hippocampal slices before or after inducing LTP.
Journal of NeuroscienceAge-dependent long-term potentiation of inhibitory synaptic transmission in rat visual cortex
119 Citations1994Yukio Komatsu
LTP of IPSP was induced by a wider range of stimulus frequencies than that capable of generating LTP of EPSPs in hippocampal CA1 and was more easily induced in developing than in mature rats, suggesting that LTP may contribute to the improvement of response selectivity of visual cortical cells through visual experience during postnatal development.
Proceedings of the National Academy of SciencesRegulation of excitatory transmission at hippocampal synapses by calbindin D28k.
118 Citations1995P S Chard, Joaquı́n Jordán +5 more
While calbindin D28k does not alter evoked neurotransmitter release at excitatory pyramidal cell synapses, this protein has a profound effect on synaptic plasticity and is shown to suppress posttetanic potentiation after infection with replication-defective adenovirus.
Trends in NeurosciencesAnoxic LTP sheds light on the multiple facets of NMDA receptors
117 Citations1994Constance Hammond, V. Cre ́pel +2 more
It is suggested that the multiple forms of NMDA receptor-dependent LTPs are determined by extracellular and intracellular modulatory sites of this receptor.
European Journal of NeuroscienceThe Relative Contribution of NMDA Receptor Channels in the Expression of Long‐term Potentiation in the Hippocampal CA1 Region
106 Citations1992Fredrik Asztély, Holger Wigström +1 more
The results suggest that, to the extent that LTP is based on an increased release of transmitter, the mechanism exhibits features distinct from those underlying other forms of enhanced release.
NeuronUp regulation of calbindin-D28K mRNA in the rat hippocampus following focal stimulation of the perforant path
103 Citations1991Daniel H. Lowenstein, Michael F. Miles +2 more
It is reported that neuronal excitation via the perforant path leads to an increased expression of calbindin-D28K mRNA within dentate granule cells, which suggests that the maintenance of Ca2+ homeostasis includes a system of feedback control at the level of gene expression.
Journal of NeurophysiologyActivation of metabotropic glutamate receptors induces long-term depression of GABAergic inhibition in hippocampus
97 Citations1993Y. B. Liu, John F. Disterhoft +1 more
The long-term enhancement of synaptic excitability in CA1 hippocampal pyramidal neurons produced by activation of metabotropic glutamate receptors was studied in rabbit hippocampal slices in vitro and a significant reduction of both components of the IPSP persisted after the washout of the drug.
NeuroscienceAsymptotic hippocampal long-term potentiation in rats does not preclude additional potentiation at later phases
95 Citations1995Uwe Frey, K. Schollmeier +2 more
It is demonstrated that, once long-term potentiation has been established, hippocampal neurons do not lose their capacity for functional plasticity during certain phases of the maintenance of long- term potentiation.
Proceedings of the National Academy of SciencesSynaptic disinhibition during maintenance of long-term potentiation in the CA1 hippocampal subfield.
94 Citations1994Armin Stelzer, Gabriel M. Simon +2 more
The present study demonstrates that the maintenance of LTP in the CA1 hippocampal subfield of guinea pigs is accompanied by impairment of type A gamma-aminobutyric acid (GABA) receptor function, particularly at apical dendritic sites of CA1 pyramidal cells.
The Journal of PhysiologySynaptic potentiation of dual‐component excitatory postsynaptic currents in the rat hippocampus.
93 Citations1995K A Clark, G.L. Collingridge
It is demonstrated that it is possible to induce LTP by high frequency stimulation after 45 min of whole‐cell recording, the first evidence, from studies of dual‐component synaptic responses, which is consistent with a presynaptic locus of expression of tetanus‐induced STP and LTP in the hippocampus.
SynapseNMDA‐dependent heterosynaptic long‐term depression in the dentate gyrus of anaesthetized rats
89 Citations1992Brian R. Christie, Wickliffe C. Abraham
The results imply that one set of common mechanisms is utilized in the induction of LTD in the dentate gyrus, whether the medial and lateral paths are activated in an associative or a non‐associative manner.
HippocampusReduction of the threshold for long‐term potentiation by prior theta‐frequency synaptic activity
86 Citations1995Brian R. Christie, David Stellwagen +1 more
The data demonstrate that the degree to which LTP is induced in the lateral path is a non‐linear function of afferent activity, and that this function, including LTP threshold, can be shifted to the left by prior synaptic activity at hippocampal theta‐rhythm frequencies.
Proceedings of the National Academy of SciencesA model of dendritic spine Ca2+ concentration exploring possible bases for a sliding synaptic modification threshold.
84 Citations1994Joshua I. Gold, Mark F. Bear
A biophysical model of an isolated dendritic spine is used to assess quantitatively the impact of changes in spine geometry, Ca2+ buffer concentration, and channel kinetics on Ca2+.
Proceedings of the National Academy of SciencesInitial synaptic efficacy influences induction and expression of long-term changes in transmission.
77 Citations1991Xinmeng Yang, D. S. Faber
The modifications in synaptic transmission caused by a certain tetanizing protocol depend upon the history of synaptic efficacy, and this last concept provides an experimental basis for theoretical models concerned with pre- and postsynaptic contributions to the regulation of synaptic plasticity.
Proceedings of the National Academy of SciencesVisual experience regulates gene expression in the developing striate cortex.
74 Citations1989Rachael L. Neve, Mark F. Bear
It is found that the mRNA transcripts of the genes for the neuronal growth-associated protein GAP43, the type II calcium/calmodulin-dependent protein kinase, and glutamic acid decarboxylase are increased in the visual cortex of animals reared in the dark.
European Journal of NeuroscienceLong‐term Depression in the Hippocampal CA1 Region is Associated with Equal Changes in AMPA and NMDA Receptor‐mediated Synaptic Potentials
48 Citations1994MY Xiao, Holger Wigström +1 more
In the present experiments using 2‐ to 3‐week‐old rats, long‐term depressions of field excitatory postsynaptic potentials mediated by amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) and by N‐ methyl‐d‐aspartate receptor channels were examined in parallel using a perfusion solution containing low concentrations of an AMPA receptor antagonist and of magnesium.
Neuroscience Lettersd-2-amino-5-phosphonovaleate blocks induction of long-term depression of the NMDA receptor-mediated synaptic component in rat hippocampus
23 Citations1993Po‐Wu Gean, Jju-Home Lin
The long-term depression of pharmacologically isolated N-methyl-D-aspartate receptor-mediated excitatory postsynaptic potential (EPSPNMDA) was studied in an in vitro slice preparation of rat hippocampus and the ESPNMDA LTD could be blocked by D-2-amino-5-phosphonovaleate suggesting that the induction of LTD requires an increase in post Synaptic Ca2+, at least in part.