The eIF2α kinase PERK limits the expression of hippocampal metabotropic glutamate receptor-dependent long-term depression

Mimi A. Trinh, Tao Ma, Hanoch Kaphzan, Aditi Bhattacharya, Marcia D. Antion, Douglas R. Cavener, Charles A. Hoeffer, Eric Klann

Research output: Contribution to journalArticle

Abstract

The proper regulation of translation is required for the expression of long-lasting synaptic plasticity. A major site of translational control involves the phosphorylation of eukaryotic initiation factor 2 α (eIF2α) by PKR-like endoplasmic reticulum (ER) kinase (PERK). To determine the role of PERK in hippocampal synaptic plasticity, we used the Cre-lox expression system to selectively disrupt PERK expression in the adult mouse forebrain. Here, we demonstrate that in hippocampal area CA1, metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD) is associated with increased eIF2α phosphorylation, whereas stimulation of early- and late-phase long-term potentiation (E-LTP and L-LTP, respectively) is associated with decreased eIF2α phosphorylation. Interesting, although PERK-deficient mice exhibit exaggerated mGluR-LTD, both E-LTP and L-LTP remained intact. We also found that mGluR-LTD is associated with a PERK-dependent increase in eIF2α phosphorylation. Our findings are consistent with the notion that eIF2α phosphorylation is a key site for the bidirectional control of persistent forms of synaptic LTP and LTD and suggest a distinct role for PERK in mGluR-LTD.

Original languageEnglish (US)
Pages (from-to)298-304
Number of pages7
JournalLearning and Memory
Volume21
Issue number5
DOIs
StatePublished - 2014

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Eukaryotic Initiation Factor-2
Metabotropic Glutamate Receptors
Phosphorylation
Neuronal Plasticity
Long-Term Synaptic Depression
Long-Term Potentiation
Prosencephalon
Endoplasmic Reticulum
PERK kinase

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience
  • Neuropsychology and Physiological Psychology
  • Medicine(all)

Cite this

The eIF2α kinase PERK limits the expression of hippocampal metabotropic glutamate receptor-dependent long-term depression. / Trinh, Mimi A.; Ma, Tao; Kaphzan, Hanoch; Bhattacharya, Aditi; Antion, Marcia D.; Cavener, Douglas R.; Hoeffer, Charles A.; Klann, Eric.

In: Learning and Memory, Vol. 21, No. 5, 2014, p. 298-304.

Research output: Contribution to journalArticle

Trinh, Mimi A. ; Ma, Tao ; Kaphzan, Hanoch ; Bhattacharya, Aditi ; Antion, Marcia D. ; Cavener, Douglas R. ; Hoeffer, Charles A. ; Klann, Eric. / The eIF2α kinase PERK limits the expression of hippocampal metabotropic glutamate receptor-dependent long-term depression. In: Learning and Memory. 2014 ; Vol. 21, No. 5. pp. 298-304.
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