Department of Biomedical Chemistry, Institute of International Health, The University of Tokyo Graduate School of Medicine, Bunkyo-ku, Tokyo 113-0033, Japan.
J Neurosci. 2012 Oct 17;32(42):14794-803. doi: 10.1523/JNEUROSCI.0793-12.2012.
In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus generates a 24 h rhythm of sleep and arousal. While neuronal spiking activity in the SCN provides a functional circadian oscillator that propagates throughout the brain, the ultradian sleep-wake state is regulated by the basal forebrain/preoptic area (BF/POA). How this SCN circadian oscillation is integrated into the shorter sleep-wake cycles remains unclear. We examined the temporal patterns of neuronal activity in these key brain regions in freely behaving rats. Neuronal activity in various brain regions presented diurnal rhythmicity and/or sleep-wake state dependence. We identified a diurnal rhythm in the BF/POA that was selectively degraded when diurnal arousal patterns were disrupted by acute brain serotonin depletion despite robust circadian spiking activity in the SCN. Local blockade of serotonergic transmission in the BF/POA was sufficient to disrupt the diurnal sleep-wake rhythm of mice. These results suggest that the serotonergic system enables the BF/POA to couple the SCN circadian signal to ultradian sleep-wake cycles, thereby providing a potential link between circadian rhythms and psychiatric disorders.
在哺乳动物中，下丘脑的视交叉上核（SCN）产生 24 小时的睡眠和觉醒节律。虽然 SCN 中的神经元尖峰活动提供了一个功能上的昼夜振荡器，可以在整个大脑中传播，但超昼夜的睡眠-觉醒状态是由基底前脑/视前区（BF/POA）调节的。SCN 昼夜振荡如何与较短的睡眠-觉醒周期整合仍然不清楚。我们在自由活动的大鼠中检查了这些关键脑区的神经元活动的时间模式。各种脑区的神经元活动呈现出昼夜节律性和/或睡眠-觉醒状态依赖性。我们发现 BF/POA 中存在昼夜节律，尽管 SCN 中的昼夜节律性尖峰活动很强，但急性大脑 5-羟色胺耗竭破坏昼夜觉醒模式时，这种节律会被选择性破坏。BF/POA 中的 5-羟色胺能传递的局部阻断足以破坏小鼠的昼夜睡眠-觉醒节律。这些结果表明，5-羟色胺能系统使 BF/POA 能够将 SCN 昼夜信号耦合到超昼夜睡眠-觉醒周期，从而为昼夜节律和精神障碍之间提供了一个潜在的联系。
