Max Planck Institute of Psychiatry, Kraepelinstrasse 2, 80804 Munich, Germany.
BMC Neurosci. 2011 Nov 2;12:110. doi: 10.1186/1471-2202-12-110.
In 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.
We 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.
The 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.
Sleep-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.
在人类中,快速眼动(REM)睡眠期间的 REM 密度在精神疾病中起着重要作用。特别是在抑郁症中,REM 密度增加是抑郁症的脆弱性标志物。在临床实践和研究测量中,REM 密度的测量高度标准化。在基础动物研究中,几乎没有工具可用于获取和系统地评估眼动数据,尽管如此,这将增加人类和动物睡眠研究之间的可比性。
我们从自由活动的小鼠中获得了标准化的脑电图(EEG)、肌电图(EMG)和眼电图(EOG)信号。EOG 电极双侧慢性植入,电极直接放置在直肌上和直肌下之间。恢复后,我们获得了四天的 EEG、EMG 和 EOG 信号。在植入过程之后,我们开发并验证了一种用于检测 REM 的眼动评分在小鼠算法(EMMA),该算法基于小波方法,将 EOG 信号的奇点检测为 REM。
清醒、非快速眼动(NREM)睡眠和快速眼动(REM)睡眠的分布与夜间啮齿动物典型分布一致,在光照期清醒时间短,NREM 睡眠时间长,而在暗期则相反。REM 睡眠相应分布。REM 睡眠中的 REM 密度明显高于 NREM 睡眠。在暗期结束时比在光期开始时检测到更多的 REM 爆发。在 REM 睡眠期间,REM 密度呈现超短周期,而在 NREM 睡眠期间,REM 密度在暗期开始时达到峰值。关于个别眼动,REM 睡眠中的 REM 持续时间较长,振幅较低。大多数 REM 和 REM 爆发与 NREM 睡眠中的微觉醒有关,但与 REM 睡眠无关。
小鼠 REM 在睡眠中的特定阶段分布与人类睡眠中的 REM 密度相对应。通过我们的方法,现在也可以在动物模型中评估 REM 密度,在急性应激后、创伤后应激障碍和抑郁症中,人类的 REM 密度会增加。现在可以利用这种关系更紧密地将动物模型与临床情况匹配,特别是在抑郁症的动物模型中。