睡眠觉醒发育及生命早期REM睡眠的调节和功能

When sleep patterns first appear in gestational age, most of the sleep cycle is rapid eye movement (REM) sleep, with little non-REM (NREM) sleep. Sleep in the term neonates is daily spend 16-18 h, as much during the night as during the day, and about equal REM and NREM in sleep cycle. In the one year old infants, REM developmentally decreases to 20% of the sleep cycle, meanwhile, NREM increases up to 80%. It has been reported that the sleep development is correspondence with the development of the brain structures and physiological function. The sleep characteristics and transitions in early animal life are similar to those of humans. However, the sleep developmental process, the role and function of early REM sleep involved in brain development, and the key component and exact time of the formation of 24-h clock-like circadian in sleep-wake cycle are unclear. A synthesized method including an analysis of sleep-wake states in infant rats, neuroanatomy, behavioral evaluation, REM sleep deprived by pharmacological and physical methods, and specific lesion of the key nuclei and pathway involved in sleep-wake regulation will be employed in the proposal project to reveal the formation of sleep states, the regular pattern of sleep-wake development, and the fundamental brain structures involved in sleep development. The project will also investigate the role of light and the suprachiasmatic nuclei in the formation of circadian rhythms in sleep-wake cycle, and the key brain structure involved in REM regulation in early life, and early REM deprivation-induced the influence on cognition, emotional behavior, sleep-wake cycle and crucial brain structure in adult. The outcome of the project will provide new insight into sleep-wake development and regulation, and fundamental theories for neonatal care and conditional interposition to preterm and term infants.

睡眠最初出现多为快动眼睡眠，非快动眼睡眠很少。睡眠在足月儿每日需16-18小时，昼夜均匀分布，快动眼与非快动眼睡眠各占50%。1岁时快动眼睡眠降为20%，非快动眼睡眠上升为80%。已有研究提示睡眠发育与脑结构及功能发育对应，多数动物早期睡眠特性和转换与人类相似。但睡眠觉醒的发育过程，早期快动眼睡眠对脑发育的作用和意义，以及睡眠觉醒周期昼夜节律形成的关键及时间仍不明。本项目将利用幼年大鼠睡眠觉醒时相解析系统，结合神经解剖、行为学评价、药理和物理学快动眼睡眠剥夺、神经核团损毁和通路阻断等手段，从细胞到整体行为揭示睡眠觉醒形成和发育规律以及关键神经结构基础；光照刺激和视交叉上核在睡眠觉醒周期昼夜节律形成中的作用；生命早期快动眼睡眠调控中枢部位，快动眼睡眠剥夺对成年大鼠认知、情绪行为、睡眠觉醒周期和关键脑结构的影响。预期结果将丰富睡眠觉醒周期发育和调节理论，为新生儿的护理和条件干预提供理论基础。

多数动物睡眠觉醒的发生和发育特征被认为与人类相似，但睡眠各时相的发育时程与规律，早期REM睡眠对脑发育的作用，以及睡眠觉醒周期昼夜节律形成的时间仍不明。本项目以新生大鼠和猫为研究对象，记录EEG、EMG、EOG等电活动，解析睡眠觉醒各时相的出现和演变，利用神经解剖学分析脑结构发育与睡眠发育的关系，剥夺新生大鼠REM睡眠观察分析成年后行为学和睡眠觉醒变化。重要结果和关键数据：（1）建立适宜幼鼠生存的连续24小时睡眠记录系统，包括适宜新生鼠的各种记录电极，按日龄定时定量哺乳系统和恒温湿抚育箱适用幼鼠连续睡眠记录，成功记录到连续的易区分EEG、EMG和EOG信号，可分析睡眠觉醒时相、结构和EEG能谱的发生发育。（2）新生大鼠睡眠主要为REM睡眠，随着年龄增加而逐渐减少，EEG delta波为特征NREM睡眠出现于生后第11天（P11），随年龄而占睡眠比率逐增并伴delta能谱增强，成为发育后期主要睡眠，各时相片段发生数随年龄减少而平均时长增加，上述变化主要发生在生后第一月。睡眠觉醒昼夜节律出现在P20。（3）制作幼鼠的全脑发育（P7-P13）图谱为识别、显微操控不同脑区及核团提供立体定位坐标。（4）解析了新生（P0-P14）大鼠新皮质及锥体细胞形态发育过程，解答了脑电与皮质结构发育关系。（5）猫P15天REM、NREM睡眠和觉醒比率分别为40%、30%和30%，随日龄增长至第61天REM减至17%，而NREM和觉醒分别增至49%和34%并接近成年各时相比率。桥-膝-枕（PGO）波P19.8天出现，提示丘脑-皮质环路建立，REM睡眠向成熟巩固期发育，结合睡眠结构和时相转换分析提示猫睡眠觉醒时相发育主要发生在生后两月。（6）剥夺幼鼠（P8-P21）REM睡眠，导致成年抑郁样行为和睡眠障碍。科学意义：研究结果丰富睡眠觉醒周期发育和调节理论，为早产儿与新生儿的护理和条件干预提供理论基础。