Role of circadian rhythm and REM sleep for memory consolidation.

Although sleep is strongly implicated in memory consolidation, the molecular basis for the role of sleep in memory is not known. It has been established that the consolidation of hippocampus-dependent memory depends on the activation of the Erk1,2 MAP kinase (MAPK) pathway which activates de novo CRE-mediated transcription and translation, two processes required for memory consolidation pathway. The activation of MAPK during memory formation and its nuclear translocation both depend upon cAMP signals generated by the calmodulin-stimulated adenylyl cyclases, type 1 and type 8 (AC1 and AC8). This signaling pathway undergoes a circadian oscillation in the hippocampus with maximal activation during REM sleep. This data supports the hypothesis that the persistence of long-term memory traces may depend upon the reactivation and circadian oscillation of the cAMP/MAP kinase/CRE transcriptional pathway in tagged neurons which reaches a maximum during REM sleep.