Hippocampal memory reactivation during sleep is correlated with specific cortical states of the Retrosplenial and Prefrontal Cortices

Episodic memories are thought to be stabilized through the coordination of cortico-hippocampal activity during sleep. However, the timing and mechanism of this coordination remain unknown. To investigate this, we studied the relationship between hippocampal reactivation and slow-wave sleep UP and Down states of the retrosplenial cortex (RTC) and prefrontal cortex (PFC). We found that hippocampal reactivation are strongly correlated with specific cortical states. Reactivation occurred during sustained cortical UP states or during the transition from UP to Down state. Interestingly, sustained UP states from the PFC were more coordinated with memory reactivation in the hippocampus, whereas hippocampal reactivation was biased to occur during the cortical UP to Down state transition of the RTC. Reactivation usually occurred within 150-200 ms of a cortical UP-state onset, indicating that a build-up of excitation during cortical UP state activity influences the probability of memory reactivation in CA1. Conversely, CA1 reactivation occurred 30-50 ms before the onset of a cortical Down state, suggesting that memory reactivation affects Down state initiation in RTC and PFC, but the effect in RTC was more robust. Our findings provide evidence that supports and highlights the complexity of bidirectional communication between cortical regions and the hippocampus during sleep.