Validation of a closed-loop sensory stimulation technique for selective sleep restriction in mice

Experimental manipulation of sleep in rodents is an important tool for analyzing the mechanisms of sleep and related disorders in humans. Sleep restriction systems have relied in the past on manual sensory stimulation and recently on more sophisticated automated means of delivering the same. The ability to monitor and track behavior through the electroencephalogram (EEG) and other modalities provides the opportunity to implement more selective sleep restriction that is targeted at particular stages of sleep with flexible control over their amount, duration, and timing. In this paper we characterize the performance of a novel tactile stimulation system operating in closed-loop to interrupt rapid eye movement (REM) sleep in mice when it is detected in real time from the EEG. Acute experiments in four wild-type mice over six hours showed that a reduction of over 50% of REM sleep was feasible without affecting non-REM (NREM) sleep. The animals remained responsive to the stimulus over the six hour duration of the experiment.