Molecular Determinants of the Spacing Effect

Abstract EN

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.