PERK Regulates Working Memory and Protein Synthesis-Dependent Memory Flexibility.
Siying Zhu, Keely Henninger, Barbara C McGrath, Douglas R Cavener
Author Information
Siying Zhu: Department of Biology, Center of Cellular Dynamics, the Pennsylvania State University, University Park, Pennsylvania, United States of America.
Keely Henninger: Department of Biology, Center of Cellular Dynamics, the Pennsylvania State University, University Park, Pennsylvania, United States of America.
Barbara C McGrath: Department of Biology, Center of Cellular Dynamics, the Pennsylvania State University, University Park, Pennsylvania, United States of America.
Douglas R Cavener: Department of Biology, Center of Cellular Dynamics, the Pennsylvania State University, University Park, Pennsylvania, United States of America.
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.
