Cited by 283Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchMemory Processes and Influences

PKMζ maintains memories by regulating GluR2-dependent AMPA receptor trafficking

Migues, Paola Virginia, Hardt, Oliver, Wu, Dong Chuan, Gamache, Karine, Sacktor, Todd Charlton, Wang, Yu Tian, Nader, Karim·2010·Nature Neuroscience

Abstract

The maintenance of long-term memory in hippocampus, neocortex and amygdala requires the persistent action of the atypical protein kinase C isoform, protein kinase Mzeta (PKMzeta). We found that inactivating PKMzeta in the amygdala impaired fear memory in rats and that the extent of the impairment was positively correlated with a decrease in postsynaptic GluR2. Blocking the GluR2-dependent removal of postsynaptic AMPA receptors abolished the behavioral impairment caused by PKMzeta inhibition and the associated decrease in postsynaptic GluR2 expression, which correlated with performance. Similarly, blocking this pathway for removal of GluR2-containing receptors from postsynaptic sites in amygdala slices prevented the reversal of long-term potentiation caused by inactivating PKMzeta. Similar behavioral results were obtained in the hippocampus for unreinforced recognition memory of object location. Together, these findings indicate that PKMzeta maintains long-term memory by regulating the trafficking of GluR2-containing AMPA receptors, the postsynaptic expression of which directly predicts memory retention.

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Crossref · 10.1038/nn.2531

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Authors
Migues, P. V., Hardt, O., Wu, D. C., Gamache, K., Sacktor, T. C., Wang, Y. T., & Nader, K.
Affiliations
  • McGill University (CA)
  • University of British Columbia (CA)
  • SUNY Downstate Health Sciences University (US)
Corresponding author
Migues, Paola Virginia
Venue
Nature Neuroscience
Published
2010-04-11
Volume
13
Issue
5
Pages
630-634
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W1974491267
Cited by
283
References
31
Citations by year
2026: 7 · 2025: 10 · 2024: 8 · 2023: 10 · 2022: 8 · 2021: 10 · 2020: 16 · 2019: 15 · 2018: 22 · 2017: 14 · 2016: 23 · 2015: 17 · 2014: 16 · 2013: 33 · 2012: 26
FWCI
20.76
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Canadian Institutes of Health Research
  • National Institute of Mental Health (MH 57068, R01MH53576, R01MH053576)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
Keywords
PKMzeta, GluR2, AMPA receptor trafficking, long-term memory, fear memory, amygdala, hippocampus, long-term potentiation, object recognition memory, memory maintenance
MeSH terms
Analysis of Variance, Animals, Avidin, Behavior, Animal, Cerebral Cortex, Conditioning, Psychological, Electroshock, Fear, Hippocampus, Male, Memory, Synaptic Transmission, Peptides, Protein Kinase C, Subcellular Fractions, Rats, Sprague-Dawley, Long-Term Potentiation, Receptors, AMPA, Patch-Clamp Techniques, Statistics, Nonparametric, Biotinylation, Rats, Long-Evans, Protein Transport, Recognition, Psychology, Freezing Reaction, Cataleptic, Rats

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