Enhancing memory via knockdown of eIF2 alpha kinase PERK: The 22nd Annual Meeting of the Israel Society for Neuroscience (ISFN) & The 2nd Bi national Italy-Israel Neuroscience Meeting

Memory consolidation is critical for the proper formation of long term memory (LTM). Translation initiation and newly synthesized proteins are crucial for memory consolidation, and protein synthesis inhibitors prevent the formation of LTM. The process of translation initiation is highly complex and involves several different factors. A major factor involved in the initiation step is the eukaryotic initation factor 2 alpha (eIF2α). eIF2α activity depends on its phosphorylation levels on specific serine residue (Ser51). Phosphorylation of Ser51 on α subunit of the eIF2 is a key regulatory mechanism in controlling translation, and it is controlled in the brain by 3 kinases (PKR, PERK, GCN-2) and phosphatases. The dephosphorylation of eIF2α is mediated via PP1c and the adaptor protein GADD34. When eIF2α is phosphorylated, translation rate is decreased and LTM is impaired and vice versa. Our research aims to decrease the phosphorylation on eIF2α in specific brain regions using viral vectors targeting the expression of the kinases, and to examine the effect of decreased phosphorylation on memory. We injected lentivirus and AAVexpressing ShRNA for PERK to the insular cortex and tested the effect on taste learning, and conditioned taste aversion (CTA).