Molecular Determinants of the Spacing Effect

• Main Authors: Faisal Naqib, Wayne S. Sossin, Carole A. Farah
• Format: Article
• Language: English
• Published: Hindawi Limited 2012-01-01
• Series: Neural Plasticity
• Online Access: http://dx.doi.org/10.1155/2012/581291

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.