Rapid eye movements during sleep in mice: High trait-like stability qualifies rapid eye movement density for characterization of phenotypic variation in sleep patterns of rodents

Abstract

BackgroundIn humans, rapid eye movements (REM) density during REM sleep plays a prominent role in psychiatric diseases. Especially in depression, an increased REM density is a vulnerability marker for depression. In clinical practice and research measurement of REM density is highly standardized. In basic animal research, almost no tools are available to obtain and systematically evaluate eye movement data, although, this would create increased comparability between human and animal sleep studies.MethodsWe obtained standardized electroencephalographic (EEG), electromyographic (EMG) and electrooculographic (EOG) signals from freely behaving mice. EOG electrodes were bilaterally and chronically implanted with placement of the electrodes directly between the musculus rectus superior and musculus rectus lateralis. After recovery, EEG, EMG and EOG signals were obtained for four days. Subsequent to the implantation process, we developed and validated an Eye Movement scoring in Mice Algorithm (EMMA) to detect REM as singularities of the EOG signal, based on wavelet methodology.ResultsThe distribution of wakefulness, non-REM (NREM) sleep and rapid eye movement (REM) sleep was typical of nocturnal rodents with small amounts of wakefulness and large amounts of NREM sleep during the light period and reversed proportions during the dark period. REM sleep was distributed correspondingly. REM density was significantly higher during REM sleep than NREM sleep. REM bursts were detected more often at the end of the dark period than the beginning of the light period. During REM sleep REM density showed an ultradian course, and during NREM sleep REM density peaked at the beginning of the dark period. Concerning individual eye movements, REM duration was longer and amplitude was lower during REM sleep than NREM sleep. The majority of single REM and REM bursts were associated with micro-arousals during NREM sleep, but not during REM sleep.ConclusionsSleep-stage specific distributions of REM in mice correspond to human REM density during sleep. REM density, now also assessable in animal models through our approach, is increased in humans after acute stress, during PTSD and in depression. This relationship can now be exploited to match animal models more closely to clinical situations, especially in animal models of depression.

Pupil Size Coupling to Cortical States Protects the Stability of Deep Sleep via Parasympathetic Modulation

“…Eye movements during tonic and phasic REM periods have been shown to have neural and muscular correlates in adult and developing mammals [ 55 , 56 , 57 ]. Currently, the state-of-the-art rodent eye-tracking systems include implanted coils or electrodes around the eye area [ 57 , 58 ]. Our technique would therefore provide a simple and noninvasive alternative for REM sleep studies.…”

The microstructure of REM sleep: Why phasic and tonic?

“…For instance, is the proportion of phasic and tonic REM microstates related to the microarchitecture of NREM phases, sleep quality, or information processing during sleep (e.g., memory consolidation)? Or does the proportion of REM microstates exhibit trait-like stability that can be linked to endophenotypes of pathological conditions [93,132]?…”

Modulation of sympathetic vasoconstriction is critical for the effects of sleep on arterial pressure in mice

“…Scoring R based only on EEG and EMG recordings is a standard practice in mice, and has been validated with concomitant electrooculographic recordings (Fulda et al . ). Sleep structure was assessed by computing the percentage of recording time spent in each wake–sleep state.…”