How coupled slow oscillations, spindles and ripples control neuronal processing and communication during human sleep

Learning and plasticity rely on fine-tuned regulation of neuronal circuits during offline periods. An unresolved puzzle is how the sleeping brain - in the absence of external stimulation or conscious effort - controls neuronal firing rates (FRs) and communication within and across circuits, supporting synaptic and systems consolidation. Using intracranial Electroencephalography (iEEG) combined with multiunit activity (MUA) recordings from the human hippocampus and surrounding medial temporal lobe (MTL) areas, we here show that governed by slow oscillation (SO) up-states, sleep spindles set a timeframe for ripples to occur. This sequential coupling leads to a stepwise increase in (i) neuronal FRs, (ii) short-latency cross-correlations among local neuronal assemblies and (iii) cross-regional MTL interactions. Triggered by SOs and spindles, ripples thus establish optimal conditions for spike-timing dependent plasticity and systems consolidation. These results unveil how the coordinated coupling of specific sleep rhythms orchestrates neuronal processing and communication during human sleep.