Neuroscience Focus Groups:
A striking feature of memory is the persistence of long-term memory which can last for periods exceeding the lifetimes of synaptic proteins. Consolidation of hippocampus-dependent memory depends upon Ca2+activation of the cAMP/Erk MAP kinase (MAPK) /CREB transcriptional pathway and de novo protein synthesis. Stimulation of MAPK activity positively regulates CREB-mediated transcription and protein synthesis during memory formation. Activation of CRE-mediated transcription in the hippocampus depends upon the calmodulin (CaM)-stimulated adenylyl cyclases which generate a cAMP signal necessary for the activation of MAPK. Our current research is based upon recent discoveries made by our lab including the discovery that that the cAMP/MAPK/ CRE transcriptional pathway undergoes a circadian oscillation in area CA1 of the hippocampus and that disruption of this signaling oscillation days after memory consolidation decreases the persistence of memory. Furthermore, we discovered that this memory consolidation pathway is activated during REM sleep relative to awake animals. This suggests that hippocampus-dependent memories are maintained over extended periods of time by periodic reactivation of CREB-mediated transcription during the circadian cycle, during sleep, and that these events are driven by cAMP activation of MAPK. We hypothesize that this critical cAMP signal is generated by CaM stimulated adenylyl cyclases. We propose that neurons stimulated during the acquisition of hippocampus-dependent memory that contribute to the initial memory trace may be periodically reactivated during the circadian cycle, during REM sleep.