Acetylcholine-gated current translates wake neuronal firing rate information into a spike timing-based code in Non-REM sleep, stabilizing neural network dynamics during memory consolidation

Sleep is critical for memory consolidation, although the exact mechanisms mediating this process are unknown. Combining reduced network models and analysis of in vivo recordings, we tested the hypothesis that neuromodulatory changes in acetylcholine (ACh) levels during non-rapid eye movement (NREM) sleep mediate stabilization of network-wide firing patterns, with temporal order of neurons’ firing dependent on their mean firing rate during wake. In both reduced models and in vivo recordings from mouse hippocampus, we find that the relative order of firing among neurons during NREM sleep reflects their relative firing rates during prior wake. Our modeling results show that this remapping of wake-associated, firing frequency-based representations is based on NREM-associated changes in neuronal excitability mediated by ACh-gated potassium current. We also show that learning-dependent reordering of sequential firing during NREM sleep, together with spike timing-dependent plasticity (STDP), reconfigures neuronal firing rates across the network. This rescaling of firing rates has been reported in multiple brain circuits across periods of sleep. Our model and experimental data both suggest that this effect is amplified in neural circuits following learning. Together our data suggest that sleep may bias neural networks from firing rate-based towards phase-based information encoding to consolidate memories.
Author summary We show that neuromodulatory changes during non-rapid eye movement (NREM) sleep generate stable spike timing relationships between neurons, the ordering of which reflects the neurons’ relative firing rates during wake. Learning-dependent ordering of firing in the hippocampus during NREM, acting in tandem with spike timing-dependent plasticity, reconfigures neuronal firing rates across the hippocampal network. This “rescaling” of neuronal firing rates has recently been reported in multiple brain circuits across periods of sleep. Together, our results suggest that the brain is remapping frequency-biased representations of information formed during wake into timing biased-representations during NREM sleep.