Sleep is defined as a reversible, natural state of reduced responsiveness to external stimuli and relative inactivity, accompanied by a loss of consciousness1. This state of inactivity has been evolutionary conserved across species against many selection pressures. This suggests that sleep holds a vital function. Multiple studies have suggested that sleep enhances both declarative and procedural memory 2,3. Consequently, memory consolidation is one of the ostensible functions of sleep. The active system consolidation hypothesis and the synaptic homeostasis hypothesis (SHY) are the two main hypotheses for this putative function of sleep. The active system consolidation model ...view middle of the document...
The proposed intracellular mechanisms will be mentioned but not discussed in great depth.
The role of slow-wave sleep in memory consolidation
Sleep consists of two main stages; slow-wave sleep (SWS) and rapid-eye-movement (REM). SWS is characterized by slow oscillations (slow wave activity), accompanied by hippocampal sharp-wave ripples (SPW-Rs) and thalamic sleep spindles. In a recent study in humans, a local increase in slow wave activity (SWA) was observed over the area of cortex that was activated in previous wake during a visuomotor task9. The degree of local increase in SWA was positively correlated with improved motor performance in the task after sleep. This is supported by evidence that boosting the slow oscillations of SWS using transcranial magnetic stimulation (TMS) over the prefrontal cortex enhanced performance in a declarative memory task10. These studies suggest a causative role for SWS in memory consolidation. Both the active systems consolidation hypothesis and SHY report essential but remarkably different roles for SWA. In the active system consolidation model, SWA in the cortex mediates a top-down reactivation of newly formed memories in the hippocampus, that are impressed on the cortex during SPW-Rs4. In contrast SWA in SHY mediates a global downscaling of synaptic weight across the cortex6.
Active systems level consolidation
The active system consolidation model proposes that sleep enhances memory consolidation by selectively reactivating certain synaptic traces in the hippocampus during SWS 4. Hippocampal replay is associated with SPW-Rs projecting to the neocortex, reflecting a redistribution of memory traces for long-term storage. Investigations of hippocampal place cells were the first to reveal this phenomenon. In a seminal study, the activity of pairs of hippocampal place cells with overlapping place fields were measured in mice11. Cells that had showed correlated firing during a spatial behavioural task in wake, displayed increased coactivation during SWS, suggesting a ‘replay’ of waking neural activity during sleep. More recently, complex replay was observed in the cortex as well as the hippocampus. High-order replay in the visual cortex and hippocampus during SWS following learning of a complex spatial task in prior wake, were observed as multi-cell spiking patterns ordered into frames12. Frames of activity in the hippocampus were temporally synchronised 50ms behind cortical frames. These results suggest that hippocampal replay is activated by cortical reactivation rather than intrinsic spontaneous activity of the hippocampus. Studies on humans trained to a spatial memory task have also reported hippocampal replay during SWS13. One caveat of these replay studies is that the subjects, particularly animal, were highly overtrained in the spatial tasks in a familiar environment. As a result, the firing patterns in pretraining sleep periods became more similar to posttraining sleep. Consequently investigations have...