Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
PLoS One. 2013 Jul 3;8(7):e68269. doi: 10.1371/journal.pone.0068269. Print 2013.
Histamine and its two receptors, histamine-gated chloride channel subunit 1 (HisCl1) and ora transientless (Ort), are known to control photoreception and temperature sensing in Drosophila. However, histamine signaling in the context of neural circuitry for sleep-wake behaviors has not yet been examined in detail. Here, we obtained mutant flies with compromised or enhanced histamine signaling and tested their baseline sleep. Hypomorphic mutations in histidine decarboxylase (HDC), an enzyme catalyzing the conversion from histidine to histamine, caused an increase in sleep duration. Interestingly, hisCl1 mutants but not ort mutants showed long-sleep phenotypes similar to those in hdc mutants. Increased sleep duration in hisCl1 mutants was rescued by overexpressing hisCl1 in circadian pacemaker neurons expressing a neuropeptide pigment dispersing factor (PDF). Consistently, RNA interference (RNAi)-mediated depletion of hisCl1 in PDF neurons was sufficient to mimic hisCl1 mutant phenotypes, suggesting that PDF neurons are crucial for sleep regulation by the histamine-HisCl1 signaling. Finally, either hisCl1 mutation or genetic ablation of PDF neurons dampened wake-promoting effects of elevated histamine signaling via direct histamine administration. Taken together, these data clearly demonstrate that the histamine-HisCl1 receptor axis can activate and maintain the wake state in Drosophila and that wake-activating signals may travel via the PDF neurons.
组胺及其两个受体，组胺门控氯离子通道亚基 1（HisCl1）和瞬时受体电位通道亚基 2（Ort），已知可控制果蝇的光感受器和温度感受。然而，在睡眠-觉醒行为的神经回路背景下，组胺信号尚未被详细研究。在这里，我们获得了组胺信号功能受损或增强的突变果蝇，并测试了它们的基础睡眠。组氨酸脱羧酶（HDC）的功能缺失突变，该酶催化组氨酸向组胺的转化，导致睡眠时间延长。有趣的是，HisCl1 突变体而不是 Ort 突变体表现出类似于 hdc 突变体的长睡眠表型。在生物钟起搏神经元中过表达 HisCl1 可挽救 HisCl1 突变体的睡眠时间延长，这些神经元表达神经肽色素分散因子（PDF）。一致地，在 PDF 神经元中 RNA 干扰（RNAi）介导的 HisCl1 耗竭足以模拟 HisCl1 突变体表型，表明 PDF 神经元对于组胺-HisCl1 信号对睡眠的调节至关重要。最后，无论是 HisCl1 突变还是 PDF 神经元的遗传消融，都通过直接给予组胺来减弱升高的组胺信号对觉醒的促进作用。总之，这些数据清楚地表明，组胺-HisCl1 受体轴可以激活和维持果蝇的觉醒状态，并且觉醒激活信号可能通过 PDF 神经元传递。
