PKMζ maintains memories by regulating GluR2-dependent AMPA receptor trafficking

Paola Virginia Migues*, Oliver Hardt, Dong Chuan Wu, Karine Gamache, Todd Charlton Sacktor, Yu Tian Wang, Karim Nader

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)630-634
Number of pages5
JournalNature Neuroscience
Volume13
Issue number5
DOIs
Publication statusPublished - May 2010

Keywords

  • Analysis of Variance
  • Animals
  • Avidin
  • Behavior, Animal
  • Biotinylation
  • Cerebral Cortex
  • Conditioning (Psychology)
  • Electroshock
  • Fear
  • Freezing Reaction, Cataleptic
  • Hippocampus
  • Long-Term Potentiation
  • Male
  • Memory
  • Patch-Clamp Techniques
  • Peptides
  • Protein Kinase C
  • Protein Transport
  • Rats
  • Rats, Long-Evans
  • Rats, Sprague-Dawley
  • Receptors, AMPA
  • Recognition (Psychology)
  • Statistics, Nonparametric
  • Subcellular Fractions
  • Synaptic Transmission

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