Gandhi Avni V, Mosser Eric A, Oikonomou Grigorios, Prober David A
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Neuron. 2015 Mar 18;85(6):1193-9. doi: 10.1016/j.neuron.2015.02.016. Epub 2015 Mar 5.
Sleep is an evolutionarily conserved behavioral state whose regulation is poorly understood. A classical model posits that sleep is regulated by homeostatic and circadian mechanisms. Several factors have been implicated in mediating the homeostatic regulation of sleep, but molecules underlying the circadian mechanism are unknown. Here we use animals lacking melatonin due to mutation of arylalkylamine N-acetyltransferase 2 (aanat2) to show that melatonin is required for circadian regulation of sleep in zebrafish. Sleep is dramatically reduced at night in aanat2 mutants maintained in light/dark conditions, and the circadian regulation of sleep is abolished in free-running conditions. We find that melatonin promotes sleep downstream of the circadian clock as it is not required to initiate or maintain circadian rhythms. Additionally, we provide evidence that melatonin may induce sleep in part by promoting adenosine signaling, thus potentially linking circadian and homeostatic control of sleep.
睡眠是一种在进化上保守的行为状态，其调节机制尚不清楚。一个经典模型认为，睡眠由稳态和昼夜节律机制调节。有几个因素参与介导睡眠的稳态调节，但昼夜节律机制背后的分子尚不清楚。在这里，我们使用由于芳基烷基胺N-乙酰转移酶2（aanat2）突变而缺乏褪黑素的动物，以表明褪黑素是斑马鱼睡眠昼夜节律调节所必需的。在光/暗条件下饲养的aanat2突变体中，夜间睡眠显著减少，在自由运行条件下，睡眠的昼夜节律调节被消除。我们发现，褪黑素在昼夜节律钟下游促进睡眠，因为它不是启动或维持昼夜节律所必需的。此外，我们提供的证据表明，褪黑素可能部分通过促进腺苷信号传导来诱导睡眠，从而潜在地将睡眠的昼夜节律和稳态控制联系起来。
