Refined Division of Sleep Stages in the Mouse Based on Distributed Deep Electrodes and Underlying Infra-Slow Oscillation.

The mouse sleep is mostly recorded with only epidural electrodes and divided simply into NREM and REM stages. With the help of distributed intracerebral triplet electrodes, we searched for possible new electrophysiological signatures to characterise more specific sleep substages within the timeframe of seconds to tens of minutes. We implanted 17 C57BL/6J male mice with double or triple wire electrodes into the hippocampus, somatosensory cortex and olfactory bulb, conventional skull screw electrodes and neck EMG electrodes. Sessions with at least 1 h of sleep of the 3-h total recording time were included in the analysis. We could identify N1, N2 and N3 stages in the mouse NREM. N2 could be further divided into N2s with spindles and N2n without spindles. Furthermore, N3 following N2n vs. N2s showed different features and were therefore coined N3s and N3n, respectively. The REM could be divided into asynchronous (aREM), synchronous (sREM) and phasic (pREM) substages. The EEG power between 5 and 30 Hz showed quasi-periodic fluctuation at an infra-slow range (0.005-0.02 Hz). The sequence of sleep stages followed reliably this fluctuation, so that the onset of N2n co-occurred with a low power, N2s halfway on the rise, aREM or N3s near the peak and sREM on the descending phase. The infra-slow fluctuation was temporarily abolished by damaging the locus coeruleus noradrenergic axons with the selective neurotoxin DSP-4 or by administration of the alpha-2 adrenergic agonist medetomidine. As a result, the brain got locked in a continuous N3-like state and no REM was present.