光通过自主感光视网膜神经节细胞调节睡眠活动

Light induced sleep is mediated by intrinsically photosensitive retinal ganglion cells

目的 利用不同基因型小鼠,探讨有无自主感光视网膜神经节细胞（ipRGCs）的小鼠在光的调节下对睡眠-觉醒活动的影响。方法 四种不同基因型小鼠,分别为野生型（C57BL/6,WT）,ipRGCs不感光型（MKO）,仅保留ipRGCs型（MO）和视杆、视锥细胞缺失且ipRGCs不感光型（TKO）。记录小鼠在12h∶12h明暗交替下24h睡眠量和觉醒量以及在关灯后1h（即21：00）给予3h光照,观察其在光照期间（21：00～24：00）睡眠量和觉醒量的变化。结果在12h∶12h明暗交替下,WT、MKO和MO小鼠的觉醒、快动眼睡眠（REM）、非快动眼睡眠（NREM）有明显的昼夜节律,并且这3种时相的分布时间差异无统计学意义;而TKO小鼠的3种时相无稳定相位,表现为自由运转。与12h∶12h明暗交替的相应时段比较,在3h光照期间,WT小鼠觉醒总量减少（P〈0.01）,REM总量增加（P〈0.01）,NREM总量增加（P〈0.01）以及总睡眠时间（TST）增加（P〈0.01）;MO小鼠觉醒总量减少（P〈0.01）,REM总量增加（P〈0.05）,NREM总量增加（P〈0.05）以及TST总量增加（P〈0.01）;MKO和TKO小鼠的3种时相均无显著变化。结论表达视黑素的ipRGCs在小鼠光诱导睡眠的过程中起重要作用。

Objective To investigate whether the light modulates sleep and wakefulness of rodents through intrinsi- cally photosensitive retinal ganglion cells （ipRGCs）. Methods Mice were divided into four groups, including C57BL/6（WT）, melanopsin knock out （MKO）, melanopsin only （MO） and coneless, rodless and melanopsin knock out （TKO）. The normal 12 h ： 12 h light dark cycle and 3 h light pulse administered at 1 h after the turning off of light （21：00） were used to detect the variation of sleep activity. Results In the normal 12 h ： 12 h light dark cycle, WT, MKO and MO mice had a regular day-night rhythm and no significant difference in wakefulness, rapid eye movement （REM） and non-rapid eye movement （NREM）. However, TKO mice could not be entrained according to the light-dark cycle and exhibited free-running rhythm. During 3 h light pulse, the amount of wakeful- ness in WT mice decreased （P 〈0. 01 ） along with an increase of REM （P 〈0.01 ）, NREM （P 〈0.01 ） and total sleep time （TST） （P 〈0. 01 ） compared with the corresponding time of the normal 12 h ： 12 h light dark cycle. MO mice exhibited a similar effect with a decrease of wakefulness （ P 〈 0.01 ） and an increase of REM, NREM and TST （P 〈0.05, P 〈 0.05, P 〈0. 01, respectively）. Both MKO and TKO mice had no significant changes for all stages during the light pulse. Conclusion Intrinsically photosensitive retinal ganglion cells play an important role in light induced sleep of mice.