Sleep has been implicated in both memory consolidation and forgetting of experiences. However, it is unclear what governs the balance between consolidation and forgetting. Here, we tested how activity-dependent processing during sleep might differentially regulate these two processes. We specifically examined how neural reactivations during non-rapid eye movement (NREM) sleep were causally linked to consolidation versus weakening of the neural correlates of neuroprosthetic skill. Strikingly, we found that slow oscillations (SOs) and delta (δ) waves have dissociable and competing roles in consolidation versus forgetting. By modulating cortical spiking linked to SOs or δ waves using closed-loop optogenetic methods, we could, respectively, weaken or strengthen consolidation and thereby bidirectionally modulate sleep-dependent performance gains. We further found that changes in the temporal coupling of spindles to SOs relative to δ waves could account for such effects. Thus, our results indicate that neural activity driven by SOs and δ waves have competing roles in sleep-dependent memory consolidation.

Systems consolidation-a process for long-term memory stabilization-has been hypothesized to occur in two stages^1-4. Whereas new memories require the hippocampus^5-9, they become integrated into cortical networks over time^10-12, making them independent of the hippocampus. How hippocampal-cortical dialogue precisely evolves during this and how cortical representations change in concert is unknown. Here, we use a skill learning task^13,14 to monitor the dynamics of cross-area coupling during non-rapid eye movement sleep along with changes in primary motor cortex (M1) representational stability. Our results indicate that precise cross-area coupling between hippocampus, prefrontal cortex and M1 can demarcate two distinct stages of processing. We specifically find that each animal demonstrates a sharp increase in prefrontal cortex and M1 sleep slow oscillation coupling with stabilization of performance. This sharp increase then predicts a drop in hippocampal sharp-wave ripple (SWR)-M1 slow oscillation coupling-suggesting feedback to inform hippocampal disengagement and transition to a second stage. Notably, the first stage shows significant increases in hippocampal SWR-M1 slow oscillation coupling in the post-training sleep and is closely associated with rapid learning and variability of the M1 low-dimensional manifold. Strikingly, even after consolidation, inducing new manifold exploration by changing task parameters re-engages hippocampal-M1 coupling. We thus find evidence for dynamic hippocampal-cortical dialogue associated with manifold exploration during learning and adaptation.

Sleep is known to promote recovery after stroke. Yet it remains unclear how stroke affects neural processing during sleep. Using an experimental stroke model in rats along with electrophysiological monitoring of neural firing and sleep microarchitecture, here we show that sleep processing is altered by stroke. We find that the precise coupling of spindles to global slow oscillations (SOs), a phenomenon that is known to be important for memory consolidation, is disrupted by a pathological increase in "isolated" local delta waves. The transition from this pathological to a physiological state-with increased spindle coupling to SO-is associated with sustained performance gains during recovery. Interestingly, post-injury sleep could be pushed toward a physiological state via a pharmacological reduction of tonic γ-aminobutyric acid (GABA). Together, our results suggest that sleep processing after stroke is impaired due to an increase in delta waves and that its restoration can be important for recovery.