PERK Regulates working memory and protein synthesis-dependent memory flexibility

Siying Zhu, Keely Henninger, Barbara C. McGrath, Douglas R. Cavener

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


PERK (EIF2AK3) is an ER-resident elF2a kinase required for memory flexibility and metabotropic glutamate receptor-dependent long-term depression, processes known to be dependent on new protein synthesis. Here we investigated PERK's role in working memory a cognitive ability that is independent of new protein synthesis, but instead is dependent on cellular Ca2+ dynamics. We found that working memory is impaired in forebrain-specific Perk knockout and pharmacologically PERK-inhibited mice. Moreover, inhibition of PERK in wild-type mice mimics the fear extinction impairment observed in forebrain-specific Perk knockout mice. Our findings reveal a novel role of PERK in cognitive functions and suggest that PERK regulates both Ca2+ -dependent working memory and protein synthesis-dependent memory flexibility.

Original languageEnglish (US)
Article numbere0162766
JournalPloS one
Issue number9
StatePublished - Sep 2016

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences
  • General


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