Translational control of hippocampal long-term synaptic plasticity and memory

old_uid3485
titleTranslational control of hippocampal long-term synaptic plasticity and memory
start_date2007/11/20
schedule11h30
onlineno
detailsInvité par Sandrine Bertrand Cnrs 5227
summaryThe late phase of long-term potentiation (LTP) and memory (LTM) requires new gene expression. The molecular mechanisms that underlie these processes are not fully understood, but there is good reason to believe that the removal of constraints on gene expression is a critical step. Phosphorylation of the translation initiation factor eIF2Éø inhibits general translation but selectively stimulates translation of ATF4, a repressor of CREB-mediated late-LTP (L-LTP) and LTM. We used a pharmacogenetic bidirectional approach to examine the role of eIF2Éø phosphorylation in synaptic plasticity and learning. In eIF2Éø heterozygous mice (eIF2Éø+/S51A) in which the phosphorylation site is mutated, L-LTP and LTM are facilitated. Moreover, a small molecule inhibitor of eIF2Éø dephosphorylation, Sal003, blocks L-LTP and memory storage. Our results provide new insight into the mechanism of mnemonic processes by showing that changes at a single phosphorylation site of a key translation initiation factor bidirectionally modulate synaptic plasticity and memory storage.
oncancelexceptionnellement un mardi
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