Referenced in: none

Automatically associated channels: TASK1

Title: Translational control of mGluR-dependent long-term depression and object-place learning by eIF2α.

Authors: Gonzalo Viana Di Prisco, Wei Huang, Shelly A Buffington, Chih-Chun Hsu, Penelope E Bonnen, Andon N Placzek, Carmela Sidrauski, Kresimir Krnjević, Randal J Kaufman, Peter Walter, Mauro Costa-Mattioli

Journal, date & volume: Nat. Neurosci., 2014 Aug , 17, 1073-82

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24974795

Abstract
At hippocampal synapses, activation of group I metabotropic glutamate receptors (mGluRs) induces long-term depression (LTD), which requires new protein synthesis. However, the underlying mechanism remains elusive. Here we describe the translational program that underlies mGluR-LTD and identify the translation factor eIF2α as its master effector. Genetically reducing eIF2α phosphorylation, or specifically blocking the translation controlled by eIF2α phosphorylation, prevented mGluR-LTD and the internalization of surface AMPA receptors (AMPARs). Conversely, direct phosphorylation of eIF2α, bypassing mGluR activation, triggered a sustained LTD and removal of surface AMPARs. Combining polysome profiling and RNA sequencing, we identified the mRNAs translationally upregulated during mGluR-LTD. Translation of one of these mRNAs, oligophrenin-1, mediates the LTD induced by eIF2α phosphorylation. Mice deficient in phospho-eIF2α-mediated translation are impaired in object-place learning, a behavioral task that induces hippocampal mGluR-LTD in vivo. Our findings identify a new model of mGluR-LTD, which promises to be of value in the treatment of mGluR-LTD-linked cognitive disorders.