Post-Training Dephosphorylation of eEF-2 Promotes Protein Synthesis for Memory Consolidation
Open Access
- 13 October 2009
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 4 (10), e7424
- https://doi.org/10.1371/journal.pone.0007424
Abstract
Memory consolidation, which converts acquired information into long-term storage, is new protein synthesis-dependent. As protein synthesis is a dynamic process that is under the control of multiple translational mechanisms, however, it is still elusive how these mechanisms are recruited in response to learning for memory consolidation. Here we found that eukaryotic elongation factor-2 (eEF-2) was dramatically dephosphorylated within 0.5–2 hr in the hippocampus and amygdala of mice following training in a fear-conditioning test, whereas genome-wide microarrays did not reveal any significant change in the expression level of the mRNAs for translational machineries or their related molecules. Moreover, blockade of NMDA receptors with MK-801 immediately following the training significantly impeded both the post-training eEF-2 dephosphorylation and memory retention. Notably, with an elegant sophisticated transgenic strategy, we demonstrated that hippocampus-specific overexpression of eEF-2 kinase, a kinase that specifically phosphorylates and hence inactivates eEF-2, significantly inhibited protein synthesis in the hippocampus, and this effects was more robust during an “ongoing” protein synthesis process. As a result, late phase long-term potentiation (L-LTP) in the hippocampus and long-term hippocampus-dependent memory in the mice were significantly impaired, whereas short-term memory and long-term hippocampus-independent memory remained intact. These results reveal a novel translational underpinning for protein synthesis pertinent to memory consolidation in the mammalian brain.Keywords
This publication has 68 references indexed in Scilit:
- Removal of FKBP12 Enhances mTOR-Raptor Interactions, LTP, Memory, and Perseverative/Repetitive BehaviorNeuron, 2008
- Systemic inhibition of mammalian target of rapamycin inhibits fear memory reconsolidationNeurobiology of Learning and Memory, 2008
- Protein synthesis inhibition and memory: Formation vs amnesiaNeurobiology of Learning and Memory, 2008
- Macromolecular synthesis, distributed synaptic plasticity, and fear conditioningNeurobiology of Learning and Memory, 2008
- Networks of neurons, networks of genes: An integrated view of memory consolidationNeurobiology of Learning and Memory, 2008
- Localization of a Stable Neural Correlate of Associative MemoryScience, 2007
- Histone Deacetylase Inhibitors Enhance Memory and Synaptic Plasticity via CREB: CBP-Dependent Transcriptional ActivationJournal of Neuroscience, 2007
- eIF2α Phosphorylation Bidirectionally Regulates the Switch from Short- to Long-Term Synaptic Plasticity and MemoryCell, 2007
- Translational control of hippocampal synaptic plasticity and memory by the eIF2α kinase GCN2Nature, 2005
- Widespread increase in brain protein synthesis following acute immobilization stress in adult rat brainNeuroscience Letters, 1996