title: PERK Regulates Working Memory and Protein Synthesis-Dependent Memory Flexibility.
abstract: PERK (EIF2AK3) is an ER-resident eIF2α 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.
authors.affiliation: Department of Biology, Center of Cellular Dynamics, the Pennsylvania State University, University Park, Pennsylvania, United States of America.
authors.forename: Siying
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Biology, Center of Cellular Dynamics, the Pennsylvania State University, University Park, Pennsylvania, United States of America.
authors.forename: Keely
authors.initials: K
authors.lastname: Henninger
authors.affiliation: Department of Biology, Center of Cellular Dynamics, the Pennsylvania State University, University Park, Pennsylvania, United States of America.
authors.forename: Barbara C
authors.initials: BC
authors.lastname: McGrath
authors.affiliation: Department of Biology, Center of Cellular Dynamics, the Pennsylvania State University, University Park, Pennsylvania, United States of America.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Cavener
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D005108:Extinction, Psychological / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D018782:Maze Learning / Q000502:physiology; D008570:Memory, Short-Term; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D016548:Prosencephalon / Q000378:metabolism / Q000502:physiology; D019892:eIF-2 Kinase / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D000225:Adenine; D007211:Indoles; D009419:Nerve Tissue Proteins; D019892:eIF-2 Kinase; C576403:7-methyl-5-(1-((3-(trifluoromethyl)phenyl)acetyl)-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo(2,3-d)pyrimidin-4-amine