title: Molecular determinants of the spacing effect.
abstract: Long-term memory formation is sensitive to the pattern of training sessions. Training distributed over time (spaced training) is superior at generating long-term memories than training presented with little or no rest interval (massed training). This spacing effect was observed in a range of organisms from invertebrates to humans. In the present paper, we discuss the evidence supporting cyclic-AMP response element-binding protein 2 (CREB), a transcription factor, as being an important molecule mediating long-term memory formation after spaced training. We also review the main upstream proteins that regulate CREB in different model organisms. Those include the eukaryotic translation initiation factor (eIF2α), protein phosphatase I (PP1), mitogen-activated protein kinase (MAPK), and the protein tyrosine phosphatase corkscrew. Finally, we discuss PKC activation and protein synthesis and degradation as mechanisms by which neurons decode the spacing intervals.
authors.affiliation: Department of Physiology, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
authors.forename: Faisal
authors.initials: F
authors.lastname: Naqib
authors.forename: Wayne S
authors.initials: WS
authors.lastname: Sossin
authors.forename: Carole A
authors.initials: CA
authors.lastname: Farah
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D006801:Humans; D008568:Memory / Q000502:physiology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D054645:Protein Phosphatase 1 / Q000502:physiology; D013997:Time Factors; D014157:Transcription Factors / Q000502:physiology
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D014157:Transcription Factors; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D054645:Protein Phosphatase 1