Interaction of Hippocampal Ripples and Cortical Slow Waves Leads to Coordinated Large-Scale Sleep Rhythm

The dialogue between cortex and hippocampus is known to be crucial for sleep dependent consolidation of long lasting memories. During slow wave sleep memory replay depends on slow oscillation (SO) and spindles in the (neo)cortex and sharp wave-ripple complexes (SWR) in the hippocampus, however, the mechanisms underlying interaction of these rhythms are poorly understood. Here, we examined the interaction between cortical SOs and hippocampal SWRs in a computational model of the hippocampo-cortico-thalamic network and compared the results with human intracranial recordings during sleep. We observed that ripple occurrence peaked following the onset of SO (Down-to-Up-state transition) and that cortical input to hippocampus was crucial to maintain this relationship. Ripples influenced the spatiotemporal structure of cortical SO and duration of the Up/Down-states. In particular, ripples were capable of synchronizing Up-to-Down state transition events across the cortical network. Slow waves had a tendency to initiate at cortical locations receiving hippocampal ripples, and these \"initiators\" were able to influence sequential reactivation within cortical Up states. We concluded that during slow wave sleep, hippocampus and neocortex maintain a complex interaction, where SOs bias the onset of ripples, while ripples influence the spatiotemporal pattern of SOs.