Long-term potentiation | Nature Neuroscience (2024)

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• Article
  23 December 2022 | Open Access

  Neocortical synaptic engrams for remote contextual memories

  Lee et al. show that the long-term storage of remote contextual memories involves progressive and synapse-specific strengthening of excitatory connections between memory engram neurons in the prefrontal cortex.

  • Ji-Hye Lee
  • , Woong Bin Kim
  • &Jun-Hyeong Cho

• Article | 17 November 2022

  Astrocytes mediate long-lasting synaptic regulation of ventral tegmental area dopamine neurons

  This study shows that burst-firing-induced astrocyte signaling potentiates glutamatergic transmission onto dopamine neurons in mouse VTA.

  • Linda Maria Requie
  • , Marta Gómez-Gonzalo
  • &Giorgio Carmignoto

• News & Views | 27 January 2022

  Puberty reverses sex differences in learning

  Adult male rodents have long been known to show stronger hippocampal long-term potentiation (LTP) and learning than females. Le et al. find that this sex difference is reversed in pre-pubescent animals, and identify a female-specific mechanism that increases LTP threshold and decreases spatial memory in females after puberty.

  • Natalie C. Tronson

• Article | 27 January 2022

  Prepubescent female rodents have enhanced hippocampal LTP and learning relative to males, reversing in adulthood as inhibition increases

  Le et al. show that, in rodents, females have lower spatial learning threshold before puberty and that sex differences in synaptic plasticity and learning thresholds reverse in the transition to adult life.

  • Aliza A. Le
  • , Julie C. Lauterborn
  • &Gary Lynch

• News & Views | 16 July 2018

  FRETting over postsynaptic PKC signaling

  Protein kinases are key regulators of excitatory synapse plasticity. In this issue, using novel optical reporters of protein kinase C (PKC) activity, Colgan et al. identify PKCα as critical for integrating NMDA receptor and neurotrophin signaling to control dendritic spine structural plasticity, synaptic potentiation, and learning and memory.

  • Mark L. Dell’Acqua
  • &Kevin M. Woolfrey

• Article | 23 April 2018

  Synaptic nanomodules underlie the organization and plasticity of spine synapses

  Hruska et al. suggest an architectural basis for NMDAR-dependent spine plasticity mediated by addition of unitary pre- and postsynaptic nanomodules that function as building blocks of synaptic organization and enable structural plasticity.

  • Martin Hruska
  • , Nathan Henderson
  • &Matthew B. Dalva

• Article | 12 February 2018

  Bidirectional and long-lasting control of alcohol-seeking behavior by corticostriatal LTP and LTD

  Addiction-related behaviors are believed to result from drug-evoked synaptic changes, but their causality is unclear. The authors show that bidirectional optogenetic modifications of synaptic strength distinctly alter alcohol-seeking behavior.

  • Tengfei Ma
  • , Yifeng Cheng
  • &Jun Wang

• Article | 11 December 2017

  The C-terminal tails of endogenous GluA1 and GluA2 differentially contribute to hippocampal synaptic plasticity and learning

  Long-lasting synaptic plasticity is regarded as a mechanism for learning and memory. Using genetically engineered mice in which the C-terminal domains of AMPA receptor subtypes are switched, the authors reveal that GluA1 and GluA2 differentially regulate synaptic plasticity and contribute to different forms of learning.

  • Zikai Zhou
  • , An Liu
  • &Zhengping Jia

  See Also

  Long-Term Synaptic PotentiationLong Term Potentiation15.11.4: Long-Term Potentiation (LTP)

• Article | 25 September 2017

  α-synuclein interacts with PrPC to induce cognitive impairment through mGluR5 and NMDAR2B

  The precise underpinnings of Parkinson's disease and other disorders associated with the accumulation of α-synuclein are unclear. This study shows that PrP^C mediates α-synuclein-associated synaptic dysfunction and memory deficits. Blocking specific events in receptor biology rescued cognitive deficits in mice, suggesting new possibilities for intervention in synucleinopathies.

  • Diana G Ferreira
  • , Mariana Temido-Ferreira
  • &Tiago F Outeiro

• Article | 13 February 2017

  Metabotropic action of postsynaptic kainate receptors triggers hippocampal long-term potentiation

  The authors show that activation of GluK2-containing kainate receptors on hippocampal neurons, by either agonist application or high-frequency synaptic stimulation, leads to a new form of NMDA-receptor-independent LTP. Induction of this form of plasticity requires the metabotropic action of postsynaptic kainate receptors, which triggers spine growth and potentiation of AMPA-receptor-mediated transmission.

  • Milos M Petrovic
  • , Silvia Viana da Silva
  • &Jeremy M Henley

• Brief Communication | 08 August 2016

  Diminished KCC2 confounds synapse specificity of LTP during senescence

  In this study, the authors show that LTP lacks synapse specificity in hippocampi of aged (21–28 months) mice, possibly resulting from diminished levels of the K⁺/Cl⁻ cotransporter KCC2 and depolarizing GABA_A receptors. The KCC2 enhancer CLP257 restored synapse specificity of LTP, providing a possible new target for repairing memory loss in senescence.

  • Isabella Ferando
  • , Guido C Faas
  • &Istvan Mody

• News & Views | 23 February 2016

  Targeting PTEN interactions for Alzheimer's disease

  Depression of AMPA receptor–mediated synaptic currents and impairment of long-term potentiation, triggered by amyloid-β, are the hallmarks of Alzheimer's pathophysiology. These dysfunctions are now linked to upregulated PDZ domain–dependent PTEN translocation to spines, contributing to cognitive deficits in model mice.

  • Samuel Frere
  • &Inna Slutsky

• Article | 18 January 2016

  PTEN recruitment controls synaptic and cognitive function in Alzheimer's models

  In this study, the authors show that PTEN alters synaptic function after PDZ-dependent recruitment into spines induced by amyloid-β. This mechanism is crucial for pathogenesis, as preventing PTEN-PDZ interactions renders neurons resistant to amyloid-β and rescues cognitive function in Alzheimer's disease models. This suggests that PTEN is a critical effector of the synaptic pathology associated with Alzheimer's disease.

  • Shira Knafo
  • , Cristina Sánchez-Puelles
  • &José A Esteban

• Article | 23 November 2015

  Synaptic adhesion molecule IgSF11 regulates synaptic transmission and plasticity

  Synaptic adhesion molecules are known to regulate synapse development, but growing evidence indicates that they also regulate synaptic function and plasticity. The authors report a novel synaptic adhesion molecule, IgSF11, that regulates excitatory synaptic transmission and plasticity through its dual interaction with the postsynaptic scaffold PSD-95 and AMPA receptors.

  • Seil Jang
  • , Daeyoung Oh
  • &Eunjoon Kim

• News & Views | 24 February 2015

  Neighborly synapses help each other out

  Cortical circuits are shaped by sensory experience. These changes have now been visualized with single-synapse resolution in vivo, revealing clustered potentiation along stretches of dendrite.

  • J Simon Wiegert
  • &Thomas G Oertner

• Article | 02 February 2015

  Visualization of NMDA receptor–dependent AMPA receptor synaptic plasticity in vivo

  Insertion of AMPA receptors into the synaptic membrane is thought to be a central mechanism for controlling experience-dependent changes in synaptic strength, yet this has never been observed in real time in the intact brain. Using two-photon imaging, Zhang and colleagues were able to provide this missing piece of information by tracking the insertion of GluA1 in spines in mouse barrel cortex neurons during repetitive whisker stimulation.

  • Yong Zhang
  • , Robert H Cudmore
  • &Richard L Huganir

• Brief Communication | 19 October 2014

  Synaptic plasticity mediating cocaine relapse requires matrix metalloproteinases

  Synaptic remodeling in the brain is dependent on the extracellular matrix remodeling mediated by zinc-dependent matrix metalloproteinases (MMPs). Using a rodent model, this study shows that the activity of MMP2 and 9 are differentially increased in the brain region nucleus accumbens after withdrawal from self-administered cocaine, during cue-induced relapse. Along with a similar response following relapse to other drugs of abuse, the study also shows that the increased MMP activity was needed for both relapse behavior and relapse-associated synaptic plasticity that included changes to the glutamate-mediated currents and dendritic spine head diameter.

  • Alexander C W Smith
  • , Yonatan M Kupchik
  • &Peter W Kalivas

• Article | 21 September 2014

  Social learning and amygdala disruptions in Nf1 mice are rescued by blocking p21-activated kinase

  Neurofibromatosis type 1 (NF1) is associated with social dysfunction in children. Here the authors show that Nf1 heterozygous mice have deficits in social memory associated with alterations in amygdala plasticity and Map kinase signaling. Global deletion or amygdala-specific pharmacological inhibition of Pak1 rescued social deficits in Nf1 heterozygous mice.

  • Andrei I Molosh
  • , Philip L Johnson
  • &Anantha Shekhar

• Brief Communication | 06 July 2014

  A spinal analog of memory reconsolidation enables reversal of hyperalgesia

  Sensitization leads to hyperalgesia and depends on mechanisms similar to those involved in memory formation. Here, Bonin and De Koninck find that hyperalgesia can be reversed by combining reactivation of peripheral afferents with spinal administration of a protein synthesis inhibitor, thereby identifying a spinal analogue of memory re-consolidation that enables erasing pain hypersensitivity.

  • Robert P Bonin
  • &Yves De Koninck

• Article | 23 March 2014

  Spine neck plasticity regulates compartmentalization of synapses

  Using time-lapse super-resolution STED imaging of dendritic spines of CA1 pyramidal neurons in mouse, the authors show dynamic structural changes to the spine neck under conditions of synaptic plasticity. The study also shows that such morphological changes can differentially regulate biochemical and electrical compartmentalization of spines and that previous characterizations of dendritic spine subtypes based on static ultrastructural morphologies may not reflect the diversity and plasticity seen in living neurons.

  • Jan Tønnesen
  • , Gergely Katona
  • &U Valentin Nägerl

• Article | 23 March 2014

  Learned spatiotemporal sequence recognition and prediction in primary visual cortex

  Here the authors report that repeated presentations of a visual sequence over a course of days causes evoked response potentiation in mouse V1 that is highly specific for stimulus order and timing. After V1 is trained to recognize a sequence, cortical activity regenerates the full sequence even when individual stimulus elements are omitted.

  • Jeffrey P Gavornik
  • &Mark F Bear

• Article | 25 August 2013

  GluA1 phosphorylation at serine 831 in the lateral amygdala is required for fear renewal

  The authors show that extinction of fear conditioning lowers the threshold for synaptic potentiation in the lateral amygdala (LA), and fear renewal-inducing stimuli induce phosphorylation of AMPAR subunit GluA1 at serine 831 in LA. Infusion of a peptide competing with Ser831-phosphorylated GluA1 into the LA blocks this low-threshold potentiation and attenuates fear renewal.

  • Sukwon Lee
  • , Beomjong Song
  • &Sukwoo Choi

• Article | 11 August 2013

  Suppression of eIF2α kinases alleviates Alzheimer's disease–related plasticity and memory deficits

  Phosphorylation of the eukaryotic initiation factor 2 α subunit (eIF2α) is increased in the brains of Alzheimer's disease patients and model mice. Here the authors show that knocking down two kinases that phosphorylate eIF2α, PERK and GCN2, rescues protein synthesis, synaptic plasticity and behavioral deficits in Alzheimer's disease model mice.

  • Tao Ma
  • , Mimi A Trinh
  • &Eric Klann

• Article | 14 July 2013

  Bidirectional NMDA receptor plasticity controls CA3 output and heterosynaptic metaplasticity

  In this paper, Hunt and colleagues provide the first demonstration of bidirectional plasticity of NMDA receptor–mediated synaptic transmission at the hippocampal mossy fiber to CA3 synapse in rats. They also show that this form of long-term plasticity can influence CA3 burst firing and spike temporal fidelity, and exert bidirectional metaplastic control over plasticity at associational-commissural synapses.

  • David L Hunt
  • , Nagore Puente
  • &Pablo E Castillo

• Article | 07 April 2013

  Noradrenaline is a stress-associated metaplastic signal at GABA synapses

  Inoue and colleagues find that stress triggers a noradrenaline-dependent metaplastic change at GABAergic synapses onto paraventricular neurons of the hypothalamus in rodents. This metaplasticity depends on mGluR1, enables these synapses to undergo long-term potentiation during afferent bursts stimulation in vitro and possibly contributes to the neuroendocrine sensitization to stress.

  • Wataru Inoue
  • , Dinara V Baimoukhametova
  • &Jaideep S Bains

• Brief Communication | 24 June 2012

  AgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors

  AgRP neurons in the hypothalamus elicit feeding behavior. Here the authors show that interfering with AgRP neuron function, either by selective knockout of Sirt1 or by early postnatal ablation, leads to increased exploratory behavior and enhanced response to cocaine, which is associated with increased forebrain dopamine levels.

  • Marcelo O Dietrich
  • , Jeremy Bober
  • &Tamas L Horvath

• Brief Communication | 01 May 2011

  NMDA receptor–dependent metaplasticity at hippocampal mossy fiber synapses

  Although they contain NMDA receptors, hippocampal mossy fiber synapses onto CA3 pyramidal cells have been reported to lack conventional NMDA receptor–dependent LTP of AMPA EPSCs. Here, the authors find that LTP of NMDA receptors serves as a metaplastic switch, making mossy fiber synapses competent to express NMDA receptor–dependent LTP of AMPA EPSCs.

  • Nelson Rebola
  • , Mario Carta
  • &Christophe Mulle

• Brief Communication | 27 March 2011

  Aβ1–42 inhibition of LTP is mediated by a signaling pathway involving caspase-3, Akt1 and GSK-3β

  Amyloid-β is known to inhibit hippocampal long-term potentiation (LTP), but the underlying molecular mechanisms are only partially understood. In this capacity, Jo and colleagues report the involvement of a signaling pathway comprised of caspase-3, Akt1 and glycogen synthase kinase-3β.

  • Jihoon Jo
  • , Daniel J Whitcomb
  • &Kwangwook Cho

• News & Views | 01 March 2010

  Timing isn't everything

  Synaptic long-term potentiation and depression are determined by the frequency and timing of coactivated synapses. A new model explains many experimental plasticity observations and allows new predictions about neural circuit function.

  • Nelson Spruston
  • &Jianhua Cang