Impaired sleep-dependent consolidation after stroke - interaction of slow waves, rehabilitation and GABA

Sleep is known to be important for promoting recovery after brain injuries such as stroke. Yet, it remains unclear how stroke affects neural processing during sleep and how to precisely enhance sleep-dependent memory consolidation after stroke, i.e., stabilize motor memories during rehabilitation. Using a rat stroke model along with long-term electrophysiological monitoring of neural firing and sleep microarchitecture, here we show that motor memory consolidation after cortical stroke is impaired. Specifically, we find that the precise coupling of spindles to global slow-oscillations (SO), 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 more physiological sleep state - with both a reduction in isolated delta waves and increased spindle coupling to SO - was found to be important for sustained performance gains with task training. Interestingly, post-stroke sleep processing could be pushed towards a more physiological state via a pharmacological reduction of tonic GABA. Together, our results indicate that sleep processing after stroke is impaired due to an increase in local delta waves and that restoration of physiological processing is important for motor memory consolidation during rehabilitation.