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Jean Claude Lacaille"Translational control of hippocampal long-term synaptic plasticity and memory"

Abstract :


The 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 eIF2α 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 eIF2α phosphorylation in synaptic plasticity and learning. In eIF2α heterozygous mice (eIF2α+/S51A) in which the phosphorylation site is mutated, L-LTP and LTM are facilitated. Moreover, a small molecule inhibitor of eIF2α 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.

Selected publications

Costa-Mattioli M, Gobert D, Stern E, Gamache K, Colina R, Cuello C, Sossin W, Kaufman R, Pelletier J, Rosenblum K, Krnjevic K, Lacaille JC, Nader K, Sonenberg N."eIF2alpha phosphorylation bidirectionally regulates the switch from short- to long-term synaptic plasticity and memory."
Cell. 2007 Apr 6;129(1):195-206.
Bourdeau ML, Morin F, Laurent CE, Azzi M, Lacaille JC. "Kv4.3-mediated A-type K+ currents underlie rhythmic activity in hippocampal interneurons."
J Neurosci. 2007 Feb 21;27(8):1942-53.

Sandrine Bertrand