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首页> 外文期刊>The European Journal of Neuroscience >Optogenetic stimulation of astrocytes in the posterior hypothalamus increases sleep at night in C57BL/6J mice
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Optogenetic stimulation of astrocytes in the posterior hypothalamus increases sleep at night in C57BL/6J mice

机译:下丘脑后部星形胶质细胞的光遗传学刺激增加了C57BL / 6J小鼠夜间的睡眠

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A distributed network of neurons regulates wake, non-rapid eye movement (NREM) sleep, and REM sleep. However, there are also glia in the brain, and there is growing evidence that neurons and astroglia communicate intimately to regulate behaviour. To identify the effect of optogenetic stimulation of astrocytes on sleep, the promoter for the astrocyte-specific cytoskeletal protein, glial fibrillary acidic protein (GFAP) was used to direct the expression of channelrhodopsin-2 (ChR2) and the linked reporter gene, enhanced yellow fluorescent protein (EYFP), in astrocytes. rAAV-GFAP-ChR2 (H134R)-EYFP or rAAV-GFAP-EYFP was microinjected (750 nL) into the posterior hypothalamus (bilateral) of mice. Three weeks later baseline sleep was recorded (0 Hz) and 24 h later optogenetic stimulation applied during the first 6 h of the lights-off period. Mice with ChR2 were given 5, 10 or 30 Hz stimulation for 6 h (10-ms pulses; 1 mW; 1 min on 4 min off). At least 36 h elapsed between the stimulation periods (5, 10, 30 Hz) and although 0 Hz was always first, the order of the other three stimulation rates was randomised. In mice with ChR2 (n = 7), 10 Hz, but not 5 or 30 Hz stimulation increased both NREM and REM sleep during the 6-h period of stimulation. Delta power did not increase. In control mice (no ChR2; n = 5), 10 Hz stimulation had no effect. This study demonstrates that direct stimulation of astrocytes powerfully induces sleep during the active phase of the sleep-wake cycle and underlines the inclusion of astrocytes in network models of sleep-wake regulation.
机译:分布的神经元网络调节觉醒,非快速眼动(NREM)睡眠和REM睡眠。然而,大脑中也有神经胶质细胞,并且越来越多的证据表明神经元和星形胶质细胞紧密地交流以调节行为。为鉴定光遗传刺激星形胶质细胞对睡眠的影响,使用星形胶质细胞特异性细胞骨架蛋白神经胶质纤维酸性蛋白(GFAP)的启动子来指导channelrhodopsin-2(ChR2)和相关报告基因的表达,增强的黄色星形胶质细胞中的荧光蛋白(EYFP)。将rAAV-GFAP-ChR2(H134R)-EYFP或rAAV-GFAP-EYFP微注射(750 nL)到小鼠的下丘脑后部(双侧)。在三周后记录基线睡眠(0 Hz),并在起燃期的前6小时内应用光遗传刺激24小时。给具有ChR2的小鼠5、10或30 Hz刺激6小时(10毫秒脉冲; 1毫瓦; 4分钟关闭1分钟)。在刺激周期(5、10、30 Hz)之间至少经过了36 h,尽管始终始终是0 Hz,但其他三个刺激率的顺序却是随机的。在具有ChR2(n = 7)的小鼠中,在刺激的6小时内,10 Hz刺激而不是5或30 Hz刺激可增加NREM和REM睡眠。三角洲的力量没有增加。在对照小鼠(无ChR2; n = 5)中,10 Hz刺激无效果。这项研究表明,星形胶质细胞的直接刺激在睡眠-觉醒周期的活跃阶段有力地诱导睡眠,并强调了星形胶质细胞在睡眠-觉醒调节的网络模型中的包含。

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