title: The eIF2α kinase PERK limits the expression of hippocampal metabotropic glutamate receptor-dependent long-term depression.
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.
authors.affiliation: Center for Neural Science, New York University, New York, New York 10003, USA.
authors.forename: Mimi A
authors.initials: MA
authors.lastname: Trinh
authors.forename: Tao
authors.initials: T
authors.lastname: Ma
authors.forename: Hanoch
authors.initials: H
authors.lastname: Kaphzan
authors.forename: Aditi
authors.initials: A
authors.lastname: Bhattacharya
authors.forename: Marcia D
authors.initials: MD
authors.lastname: Antion
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Cavener
authors.forename: Charles A
authors.initials: CA
authors.lastname: Hoeffer
authors.forename: Eric
authors.initials: E
authors.lastname: Klann
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D055592:Biophysical Phenomena / Q000187:drug effects / Q000235:genetics; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D004558:Electric Stimulation; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism*
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D004268:DNA-Binding Proteins; D008734:Methoxyhydroxyphenylglycol; D008869:Microtubule-Associated Proteins; D018094:Receptors, Metabotropic Glutamate; D014157:Transcription Factors; D019892:eIF-2 Kinase; C103652:Elf2 protein, mouse; C079240:Mtap2 protein, mouse; C010117:3,4-dihydroxyphenylglycol
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