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bioRxiv · 10.1101/2025.09.15.676366

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

Shin, J. D.·Miller, P.·Satchell, M.·Jadhav, S. P.
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Abstract

REM (rapid eye movement) and non-REM (NREM) sleep stages contribute to 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 oscillation (HFO) chains in REM sleep during consolidation of recently acquired spatial memory. High-density tetrode recordings in hippocampal area CA1 and PFC reveal that REM cortical HFOs occur in characteristic chains that are phase modulated by theta oscillations, corresponding to increased CA1-PFC theta coherence and delineating periods of enhanced hippocampal-cortical communication. REM HFO chains sequentially organize sparse PFC ensemble reactivation of behavioral activity during periods of local suppression, distinct from widespread reactivation bursts during NREM ripple oscillations. REM HFO chains also preferentially engage CA1 neuronal populations that demonstrate a shift in their preferred theta-phase from behavior to REM sleep. CA1 neuronal activation during REM HFO chains was correlated with CA1 activity suppression during NREM PFC ripples, and linked to differential changes in CA1 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 HFO chains. Overall, these findings establish a role for PFC high-frequency oscillations in regulating distinct dual sleep stage reactivation patterns.

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Shin, J. D., Miller, P., Satchell, M., Jadhav, S. P.. 2025-09-17. REM sleep prefrontal ripple chains mediate distinct cortical-hippocampal reactivation patterns compared to NREM ripples. https://doi.org/10.1101/2025.09.15.676366

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