REM sleep prefrontal ripple chains mediate distinct cortical-hippocampal reactivation patterns compared to NREM ripples

REM (rapid eye movement) and non-REM (NREM) sleep stages are both critical for systems memory consolidation in hippocampal-cortical circuits. However, the physiological mechanisms underlying REM memory processes remain relatively unclear compared to NREM memory reactivation. Here we report, in rodents, the existence of prefrontal cortical (PFC) high-frequency ripple chains in REM sleep during consolidation of recently acquired spatial memory. High-density tetrode recordings in hippocampal area CA1 and PFC reveal that, in contrast to NREM cortical ripples, REM cortical ripples occur in characteristic chains that are phase modulated by theta oscillations in phasic REM sleep, corresponding to increased CA1-PFC theta coherence and delineating periods of enhanced hippocampal-cortical communication. REM ripple chains sequentially organize sparse PFC ensemble reactivation of behavioral activity during periods of local suppression, distinct from widespread reactivation bursts during NREM ripples. REM ripple chains also selectively engage CA1 neuronal populations that shift preferred theta-phase from behavior to REM sleep. Co-reactivation of PFC and CA1 neurons during REM ripple chains was linked to CA1 activity suppression during NREM PFC ripples, and to differential changes in CA1 neuronal firing rates in sleep, suggesting REM-driven regulation of hippocampal excitability. A cortical network model incorporating the effects of acetylcholine can reproduce the distinct REM and NREM activity patterns, providing a mechanistic basis for widespread coactivity during NREM cortical ripples, compared to sparse, temporally extended reactivation on a background of local suppression during REM ripple chains. Overall, these findings establish a role for PFC ripples in regulating distinct dual sleep stage cortical-hippocampal reactivation patterns.