Pharmacological analysis of sleep consolidation mechanisms in mammals

Changes in the sleep/wake consolidation (whether the duration of sleep/wake is sustained or the transition between sleep and wake is frequently observed, or in other words fragmented) are one of the parameters describing sleep/wake dynamics. The disturbance of sleep/wake consolidation occurs in several psychiatric disorders. For example, major depressive disorder patients often suffer from sleep fragmentation that severely disrupts patients' quality of life. Although many studies have reported brain regions/neurons responsible for total sleep/wake duration in mammals, those responsible for the sleep/wake consolidation still remain unclear. We have pharmacologically induced sleep/wake consolidation disturbance in mice. To measure the sleep/wake status noninvasively, we used "Snappy Sleep Stager (SSS)" (Sunagawa et al, Cell Rep., 2016) method based on the respiratory waveform analysis. Sleep/wake consolidation was quantitatively evaluated by calculating the transition probability that a sleep/wake state switches to the other one. Interestingly, pharmacological perturbation on wild-type mice revealed that changes in sleep/wake consolidation can be independent of changes in the total sleep/wake duration, suggesting that the underlying mechanisms for controlling sleep/wake consolidation and total sleep/wake duration are independent of each other. We also found that several mutant mice impaired/enhanced Ca2+ dependent hyperpolarization showed changes in sleep/wake consolidation as well as changes in total sleep/wake duration (Tatsuki et al, Neuron, 2016). In-depth analysis of these mice will leads to the understanding of the sleep/wake consolidation controlling mechanisms in mammals.