Satchell, M. | Search bioRxiv

bioRxiv2025

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 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.

neuroscience↗

bioRxiv2023

Distinct roles for sequential NREM and REM acetylcholine-regulated states during sleep-dependent memory consolidation

Across vertebrate species, sleep consists of repeating cycles of NREM followed by REM. However, the respective functions of NREM, REM, and their stereotypic cycling pattern are not well understood. Using a simplified biophysical network model, we show that NREM and REM sleep can play differential and critical roles in memory consolidation primarily regulated, based on state-specific changes in cholinergic signaling. Within this network, decreasing and increasing muscarinic acetylcholine (ACh) signaling during bouts of NREM and REM, respectively, differentially alters neuronal excitability and excitatory/inhibitory balance. During NREM, deactivation of inhibitory neurons leads to network-wide disinhibition and bursts of synchronized activity led by firing in engram neurons. These features strengthen connections from the original engram neurons to less-active network neurons. In contrast, during REM, an increase in network inhibition suppresses firing in all but the most-active excitatory neurons, leading to competitive strengthening/pruning of the memory trace. We tested the predictions of the model against in vivo recordings from mouse hippocampus during active sleep-dependent memory storage. Consistent with modeling results, we find that functional connectivity between CA1 neurons changes differentially at transition from NREM to REM sleep during learning. Returning to the model, we find that an iterative sequence of state-specific activations during NREM/REM cycling is essential for memory storage in the network, serving a critical role during simultaneous consolidation of multiple memories. Together these results provide a testable mechanistic hypothesis for the respective roles of NREM and REM sleep, and their universal relative timing, in memory consolidation. Significance statementUsing a simplified computational model and in vivo recordings from mouse hippocampus, we show that NREM and REM sleep can play differential roles in memory consolidation. The specific neurophysiological features of the two sleep states allow for expansion of memory traces (during NREM) and prevention of overlap between different memory traces (during REM). These features are likely essential in the context of storing more than one new memory simultaneously within a brain network.

neuroscience↗