A time window for memory consolidation during NREM sleep revealed by cAMP oscillation

Memory formation requires specific neural activity in coordination with intracellular signaling mediated by second messengers such as cyclic adenosine monophosphate (cAMP). However, the real-time dynamics of cAMP remain largely unknown. Here, using a genetically encoded cAMP sensor with high temporal resolution, we found neural-activity-dependent rapid cAMP elevation during learning. Interestingly, in slow-wave sleep, during which memory consolidation occurs, the cAMP level in mice was anti-correlated with neural activity and exhibited norepinephrine β1 receptor-dependent infra-slow oscillations that were synchronized across the hippocampus and cortex. Furthermore, the hippocampal-cortical interactions increased during the narrow time-window of the peak cAMP level; suppressing hippocampal activity specifically during this window impaired spatial memory consolidation. Thus, hippocampal-dependent memory consolidation occurs within a specific time window of high cAMP activity during slow-wave sleep.