Identification of a dopamine pathway that regulates sleep and arousal in Drosophila

Identification of a dopamine pathway that regulates sleep and arousal in Drosophila
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DOI:
10.1038/nn.3238
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发表时间:
2012-11-01
影响因子:
25
通讯作者:
Kume, Kazuhiko
Kume, Kazuhiko
中科院分区:
医学1区
文献类型:
--
作者:
Ueno, Taro;Tomita, Jun;Kume, Kazuhiko

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睡眠是维持包括记忆在内的生理功能所必需的,并且在不同物种中受到单胺的调节。多巴胺转运蛋白(DAT)突变增强多巴胺信号会减少睡眠,但对此负责的潜在多巴胺回路仍然未知。我们发现果蝇背侧扇形体(dFSB)中的D1多巴胺受体(DA1)介导多巴胺的唤醒效应。DAT突变体的短睡眠表型被DA1(也称为DopR)基因中的额外突变完全挽救,但野生型DA1在dFSB中的表达恢复了短睡眠表型。我们发现了多巴胺神经元和dFSB神经元之间的解剖学和生理学联系。最后,我们使用镶嵌分析与抑制标记,发现一个单一的多巴胺神经元投射到FSB激活唤醒。这些结果表明,局部多巴胺通路调节睡眠。
Sleep is required to maintain physiological functions, including memory, and is regulated by monoamines across species. Enhancement of dopamine signals by a mutation in the dopamine transporter (DAT) decreases sleep, but the underlying dopamine circuit responsible for this remains unknown. We found that the D1 dopamine receptor (DA1) in the dorsal fan-shaped body (dFSB) mediates the arousal effect of dopamine in Drosophila. The short sleep phenotype of the DAT mutant was completely rescued by an additional mutation in the DA1 (also known as DopR) gene, but expression of wild-type DA1 in the dFSB restored the short sleep phenotype. We found anatomical and physiological connections between dopamine neurons and the dFSB neuron. Finally, we used mosaic analysis with a repressive marker and found that a single dopamine neuron projecting to the FSB activated arousal. These results suggest that a local dopamine pathway regulates sleep.