The eIF2α kinase PERK limits the expression of hippocampal metabotropic glutamate receptor-dependent long-term depression. Journal Article uri icon



  • 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.

publication date

  • April 16, 2014

has subject area

has restriction

  • gold

Date in CU Experts

  • October 31, 2014 4:45 AM

Full Author List

  • Trinh MA; Ma T; Kaphzan H; Bhattacharya A; Antion MD; Cavener DR; Hoeffer CA; Klann E

author count

  • 8

Other Profiles

Electronic International Standard Serial Number (EISSN)

  • 1549-5485

Additional Document Info

start page

  • 298

end page

  • 304


  • 21


  • 5