Chung Brian Y, Kilman Valerie L, Keath J Russel, Pitman Jena L, Allada Ravi
Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA.
Curr Biol. 2009 Mar 10;19(5):386-90. doi: 10.1016/j.cub.2009.01.040. Epub 2009 Feb 19.
Sleep is regulated by a circadian clock that times sleep and wake to specific times of day and a homeostat that drives sleep as a function of prior wakefulness. To analyze the role of the circadian clock, we have used the fruit fly Drosophila. Flies display the core behavioral features of sleep, including relative immobility, elevated arousal thresholds, and homeostatic regulation. We assessed sleep-wake modulation by a core set of circadian pacemaker neurons that express the neuropeptide PDF. We find that disruption of PDF function increases sleep during the late night in light:dark and the first subjective day of constant darkness. Flies deploy genetic and neurotransmitter pathways to regulate sleep that are similar to those of their mammalian counterparts, including GABA. We find that RNA interference-mediated knockdown of the GABA(A) receptor gene, Resistant to dieldrin (Rdl), in PDF neurons reduces sleep, consistent with a role for GABA in inhibiting PDF neuron function. Patch-clamp electrophysiology reveals GABA-activated picrotoxin-sensitive chloride currents on PDF+ neurons. In addition, RDL is detectable most strongly on the large subset of PDF+ pacemaker neurons. These results suggest that GABAergic inhibition of arousal-promoting PDF neurons is an important mode of sleep-wake regulation in vivo.
睡眠受昼夜节律时钟和稳态调节器调节，昼夜节律时钟将睡眠和清醒时间安排在一天中的特定时段，稳态调节器则根据先前的清醒状态驱动睡眠。为了分析昼夜节律时钟的作用，我们使用了果蝇。果蝇表现出睡眠的核心行为特征，包括相对不动、觉醒阈值升高和稳态调节。我们评估了一组表达神经肽PDF的核心昼夜节律起搏器神经元对睡眠-觉醒的调节作用。我们发现，PDF功能的破坏会增加光暗周期中深夜以及持续黑暗的第一个主观日的睡眠时间。果蝇利用与哺乳动物类似的遗传和神经递质途径来调节睡眠，包括GABA。我们发现，通过RNA干扰介导在PDF神经元中敲低GABA(A)受体基因狄氏剂抗性（Rdl）会减少睡眠，这与GABA在抑制PDF神经元功能中的作用一致。膜片钳电生理学揭示了PDF+神经元上GABA激活的对苦味毒敏感的氯离子电流。此外，在大部分PDF+起搏器神经元中可最强检测到RDL。这些结果表明，GABA能抑制促进觉醒的PDF神经元是体内睡眠-觉醒调节的一种重要模式。
