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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

DOI 10.1038/nn.2531

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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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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
ORCID: Hardt, Oliver
Wu, Dong Chuan
Sacktor, Todd Charlton
Wang, Yu Tian
Nader, Karim
Venue: Nature Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2010-04-11
Volume: 13
Issue: 5
Pages: 630-634
ISSN: 1097-6256 (ISSN-L)
1546-1726
DOI: 10.1038/nn.2531
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
Licence: www.springer.com/tdm (tdm)
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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PKMζ maintains memories by regulating GluR2-dependent AMPA receptor trafficking

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