PERK Regulates working memory and protein synthesis-dependent memory flexibility

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

doi:10.1371/journal.pone.0162766

PERK Regulates working memory and protein synthesis-dependent memory flexibility

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

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

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 language	English (US)
Article number	e0162766
Journal	PloS one
Volume	11
Issue number	9
DOIs	https://doi.org/10.1371/journal.pone.0162766
State	Published - Sep 2016

All Science Journal Classification (ASJC) codes

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

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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.",

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AU - McGrath, Barbara C.

AU - Cavener, Douglas R.

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PERK Regulates working memory and protein synthesis-dependent memory flexibility

Abstract

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