PERK Regulates working memory and protein synthesis-dependent memory flexibility

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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
Volume11
Issue number9
DOIs
StatePublished - Sep 2016

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Short-Term Memory
protein synthesis
Prosencephalon
Data storage equipment
Metabotropic Glutamate Receptors
Proteins
Aptitude
mice
Knockout Mice
Cognition
Fear
Phosphotransferases
brain
calcium
Depression
fearfulness
cognition
phosphotransferases (kinases)
extinction

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

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PERK Regulates working memory and protein synthesis-dependent memory flexibility. / Zhu, Siying; Henninger, Keely; McGrath, Barbara C.; Cavener, Douglas R.

In: PloS one, Vol. 11, No. 9, e0162766, 09.2016.

Research output: Contribution to journalArticle

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