GABAB receptors play an essential role in maintaining sleep during the second half of the night in Drosophila melanogaster
GABAB receptors play an essential role in maintaining sleep during the second half of the night in Drosophila melanogaster
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DOI：
10.1242/jeb.085563
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发表时间：
2013-10-01
影响因子：
2.8
通讯作者：
Helfrich-Foerster, Charlotte
中科院分区：
文献类型：
--
作者：
Gmeiner, Florian;Kolodziejczyk, Agata;Helfrich-Foerster, Charlotte
GABA能信号对人类和苍蝇的正常睡眠很重要。在这里，我们通过关注果蝇慢代谢性GABA(B)受体在果蝇中的作用来推进对GABA能调节日常睡眠模式的当前理解。我们询问了GABA(B)-R2受体是否是睡眠调节中的调节元件，以及已经确定的快速电离性RDL GABA(A)受体。通过免疫细胞化学和基于报告基因的技术，我们发现色素分散因子(PDF)阳性的腹外侧钟神经元(LNV)表达GABA(B)-R2受体。RNAi下调大的PDF神经元(L-LNV)的GABA(B)-R2受体，减少了后半夜的睡眠维持，而以前被证明依赖于离子型RDL GABA(A)受体的夜间睡眠潜伏期保持不变。我们的结果证实了L-LNV神经元是黑腹金丝猴睡眠回路的重要组成部分，也确认了GABA(B)-R2受体是迄今为止缺失的GABA信号中对睡眠维持至关重要的成分。尽管对睡眠有显著的影响，但我们没有观察到GABA(B)-R2受体下调的果蝇的昼夜行为的任何变化，这表明通过L-LNV神经元对睡眠维持的调节不依赖于它们在昼夜时钟电路中的功能。
GABAergic signalling is important for normal sleep in humans and flies. Here we advance the current understanding of GABAergic modulation of daily sleep patterns by focusing on the role of slow metabotropic GABA(B) receptors in the fruit fly Drosophila melanogaster. We asked whether GABA(B)-R2 receptors are regulatory elements in sleep regulation in addition to the already identified fast ionotropic Rdl GABA(A) receptors. By immunocytochemical and reporter-based techniques we show that the pigment dispersing factor (PDF)-positive ventrolateral clock neurons (LNv) express GABA(B)-R2 receptors. Downregulation of GABA(B)-R2 receptors in the large PDF neurons (l-LNv) by RNAi reduced sleep maintenance in the second half of the night, whereas sleep latency at the beginning of the night that was previously shown to depend on ionotropic Rdl GABA(A) receptors remained unaltered. Our results confirm the role of the l-LNv neurons as an important part of the sleep circuit in D. melanogaster and also identify the GABA(B)-R2 receptors as the thus far missing component in GABA-signalling that is essential for sleep maintenance. Despite the significant effects on sleep, we did not observe any changes in circadian behaviour in flies with downregulated GABA(B)-R2 receptors, indicating that the regulation of sleep maintenance via l-LNv neurons is independent of their function in the circadian clock circuit.