MAPK, CREB and zif268 are all required for the consolidation of recognition memory.
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 (MAPK/ERK) signalling in the regulation of gene transcription in neurons. Here, we briefly review experiments that have shown MAPK/ERK, 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.
Bozon
Bruno
B
Laboratoire de Neurobiologie de l'Apprentissage, de la Mémoire et de la Communication, CNRS UMR 8620, Université Paris-Sud, 91405 Orsay, France.
Kelly
Aine
A
Josselyn
Sheena A
SA
Silva
Alcino J
AJ
Davis
Sabrina
S
Laroche
Serge
S
D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D051766:Early Growth Response Protein 1; D004789:Enzyme Activation / Q000502:physiology; D017874:Immediate-Early Proteins; D017774:Long-Term Potentiation / Q000502:physiology; D008568:Memory / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D021641:Recognition, Psychology / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D014157:Transcription Factors; D020928:Mitogen-Activated Protein Kinases