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Cortical Layer 6b Mediates State-Dependent Changes in Brain Activity and Effects of Orexin on Waking and Sleep

crossref(2024)

University of Oxford | Toho University | MRC Nucleic Acid Therapy Accelerator

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Abstract
One of the most distinctive features of the mammalian cerebral cortex is its laminar structure. Of all cortical layers, layer 6b (L6b) is by far the least-studied, despite exhibiting direct sensitivity to orexin and having widespread connectivity, suggesting an important role in regulating cortical oscillations and brain state. We performed chronic electroencephalogram (EEG) recordings in mice in which a subset of L6b neurons was conditionally silenced, during undisturbed conditions, after sleep deprivation (SD), and after intracerebroventricular (ICV) administration of orexin. While the total amount of waking and sleep or the response to SD were not altered, L6b-'silenced' mice showed a slowing of theta-frequency (6-9 Hz) during wake and REM sleep, and a marked reduction of total EEG power, especially in NREM sleep. The infusion of orexin A increased wakefulness in both genotypes, but the effect was more pronounced in L6b-silenced mice, while the increase in theta-activity by orexin B was attenuated in L6b silenced animals. In summary, we show the role of cortical L6b in state-dependent brain oscillations and global vigilance state control, which could be mediated by orexinergic neurotransmission. Our findings provide new insights in the understanding of abnormal regulation of arousal states in neurodevelopmental and anxiety disorders. ### Competing Interest Statement The authors have declared no competing interest.
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要点】:研究发现大脑皮层6b层在调节脑状态依赖的脑活动变化和调节觉醒与睡眠的食欲素作用中具有重要作用。

方法】:通过在特定条件下对小鼠的6b层神经元进行条件性沉默,并记录慢性脑电图(EEG)。

实验】:实验中,对未打扰条件下、睡眠剥夺后以及脑室内给予食欲素的小鼠进行了EEG记录,使用的数据集为实验过程中收集的EEG数据。结果显示,6b层沉默的小鼠在清醒和REM睡眠期间theta频率减慢,NREM睡眠期间总脑电图功率显著降低,且对食欲素A的反应增强,对食欲素B的theta活动增强作用减弱。