The eIF2α kinase PERK limits the expression of hippocampal metabotropic glutamate receptor-dependent long-term depression
- Mimi A. Trinh1,6,
- Tao Ma1,6,
- Hanoch Kaphzan1,4,
- Aditi Bhattacharya1,
- Marcia D. Antion2,
- Douglas R. Cavener3,
- Charles A. Hoeffer1,5 and
- Eric Klann1,7
- 1Center for Neural Science, New York University, New York, New York 10003, USA
- 2Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
- 3Department of Biology, University Park, Pennsylvania State University, University Park, Pennsylvania 16802, USA
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↵6 These authors contributed equally to this work.
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.
Footnotes
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↵7 Corresponding author
E-mail eklann{at}cns.nyu.edu
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Article is online at http://www.learnmem.org/cgi/doi/10.1101/lm.032219.113.
- Received June 23, 2013.
- Accepted March 10, 2014.
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