Cell ( IF 45.5 ) Pub Date : 2023-12-08 , DOI: 10.1016/j.cell.2023.11.012 Bing Li 1 , Chenyan Ma 1 , Yun-An Huang 2 , Xinlu Ding 1 , Daniel Silverman 1 , Changwan Chen 1 , Dana Darmohray 1 , Lihui Lu 1 , Siqi Liu 1 , Gabriel Montaldo 2 , Alan Urban 2 , Yang Dan 1
Conscious perception is greatly diminished during sleep, but the underlying circuit mechanism is poorly understood. We show that cortical ignition—a brain process shown to be associated with conscious awareness in humans and non-human primates—is strongly suppressed during non-rapid-eye-movement (NREM) sleep in mice due to reduced cholinergic modulation and rapid inhibition of cortical responses. Brain-wide functional ultrasound imaging and cell-type-specific calcium imaging combined with optogenetics showed that activity propagation from visual to frontal cortex is markedly reduced during NREM sleep due to strong inhibition of frontal pyramidal neurons. Chemogenetic activation and inactivation of basal forebrain cholinergic neurons powerfully increased and decreased visual-to-frontal activity propagation, respectively. Furthermore, although multiple subtypes of dendrite-targeting GABAergic interneurons in the frontal cortex are more active during wakefulness, soma-targeting parvalbumin-expressing interneurons are more active during sleep. Chemogenetic manipulation of parvalbumin interneurons showed that sleep/wake-dependent cortical ignition is strongly modulated by perisomatic inhibition of pyramidal neurons.
中文翻译:
NREM 睡眠期间抑制额叶皮层点火的电路机制
睡眠期间,意识知觉会大大减弱,但其背后的回路机制却知之甚少。我们发现,皮质点火(一种与人类和非人类灵长类动物的意识意识相关的大脑过程)在小鼠非快速眼动(NREM)睡眠期间受到强烈抑制,原因是胆碱能调节减少和快速抑制皮质反应。全脑功能超声成像和细胞类型特异性钙成像与光遗传学相结合表明,由于额叶锥体神经元的强烈抑制,NREM睡眠期间从视觉到额叶皮层的活动传播显着减少。基底前脑胆碱能神经元的化学遗传学激活和失活分别有力地增加和减少了视觉到额叶活动的传播。此外,虽然额叶皮层中靶向树突的 GABA 能中间神经元的多种亚型在清醒时更加活跃,但靶向表达小白蛋白的体细胞中间神经元在睡眠期间更加活跃。小清蛋白中间神经元的化学遗传学操作表明,睡眠/觉醒依赖性皮质点火受到锥体神经元的体周抑制的强烈调节。