| First Author | Di Prisco GV | Year | 2014 |
| Journal | Nat Neurosci | Volume | 17 |
| Issue | 8 | Pages | 1073-82 |
| PubMed ID | 24974795 | Mgi Jnum | J:214966 |
| Mgi Id | MGI:5604304 | Doi | 10.1038/nn.3754 |
| Citation | Di Prisco GV, et al. (2014) Translational control of mGluR-dependent long-term depression and object-place learning by eIF2alpha. Nat Neurosci 17(8):1073-82 |
| abstractText | 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 eIF2alpha as its master effector. Genetically reducing eIF2alpha phosphorylation, or specifically blocking the translation controlled by eIF2alpha phosphorylation, prevented mGluR-LTD and the internalization of surface AMPA receptors (AMPARs). Conversely, direct phosphorylation of eIF2alpha, 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 eIF2alpha phosphorylation. Mice deficient in phospho-eIF2alpha-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. |
