MAPK, CREB and zif268 are all required for the consolidation of recognition memory

被引:242
作者
Bozon, B
Kelly, A
Josselyn, SA
Silva, AJ
Davis, S
Laroche, S
机构
[1] Univ Paris 11, Lab Neurobiol Apprentissage Memoire & Commun, CNRS, UMR 8620, F-91405 Orsay, France
[2] Univ Dublin Trinity Coll, Dept Physiol, Dublin 2, Ireland
[3] Univ Calif Los Angeles, Dept Neurobiol, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90095 USA
[5] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA
[6] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA
关键词
learning; long-term potentiation; synaptic plasticity; hippocampus; gene expression; transgenic mice;
D O I
10.1098/rstb.2002.1224
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
There has been nearly a century of interest in the idea that encoding and storage of information in the brain requires changes in the efficacy of synaptic connections between neurons that are activated during learning. Recent research into the molecular mechanisms of long-term potentiation (LTP) has brought about new knowledge that has provided valuable insights into the neural mechanisms of memory storage. The evidence indicates that rapid activation of the genetic machinery can be a key mechanism underlying the enduring modification of neural networks required for the stability of memories. In recent years, a wealth of experimental data has highlighted the importance of mitogen-activated protein kinase/ extracellular signal-regulated kinase (A/LAPK/ERK) signalling in the regulation of gene transcription in neurons. Here, we briefly review experiments that have shown MAMERK, cAMP response element-binding protein (CREB) and the immediate early gene (IEG) zif268 are essential components of a signalling cascade required for the expression of late phase LTP and of certain forms of long-term memory. We also present experiments in which we have assessed the role of these three molecules in recognition memory. We show that pharmacological blockade of MAPK/ERK phosphorylation, functional inactivation of CREB in an inducible transgenic mouse and inactivation of zif268 in a mutant mouse result in a similar deficit in long-term recognition memory. In the continuing debate about the role of LTP mechanisms in memory, these findings provide an important complement to the suggestion that synaptic changes brought about by LTP and memory consolidation and storage share, at least in part, common underlying molecular mechanisms.
引用
收藏
页码:805 / 814
页数:10
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