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果蝇多动突变体的睡眠减少且记忆受损。

Drosophila Hyperkinetic mutants have reduced sleep and impaired memory.

作者信息

Bushey Daniel, Huber Reto, Tononi Giulio, Cirelli Chiara

机构信息

Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin 53719, USA.

出版信息

J Neurosci. 2007 May 16;27(20):5384-93. doi: 10.1523/JNEUROSCI.0108-07.2007.

Abstract

In mammals, sleep is thought to be important for health, cognition, and memory. Fruit flies share most features of mammalian sleep, and a recent study found that Drosophila lines carrying loss-of-function mutations in Shaker (Sh) are short sleeping, suggesting that the Sh current plays a major role in regulating daily sleep amount. The Sh current is potentiated by a beta modulatory subunit coded by Hyperkinetic (Hk). Here, we demonstrate that severe loss-of-function mutations of Hk reduce sleep and do so primarily by affecting the Sh current. Moreover, we prove, using a transgenic approach, that a wild-type copy of Hk is sufficient to restore normal sleep. Furthermore, we show that short-sleeping Hk mutant lines have a memory deficit, whereas flies carrying a weaker hypomorphic Hk allele have normal sleep and normal memory. By comparing six short-sleeping Sh lines with two normal sleeping ones, we also found that only alleles that reduce sleep also impair memory. These data identify a gene, Hk, which is necessary to maintain normal sleep, and provide genetic evidence that short sleep and poor memory are linked.

摘要

在哺乳动物中,睡眠被认为对健康、认知和记忆很重要。果蝇具有哺乳动物睡眠的大多数特征,最近一项研究发现,携带震颤基因(Sh)功能丧失突变的果蝇品系睡眠时间短,这表明Sh电流在调节每日睡眠量中起主要作用。Sh电流由超动力基因(Hk)编码的β调节亚基增强。在此,我们证明Hk的严重功能丧失突变会减少睡眠,并且主要是通过影响Sh电流来实现的。此外,我们通过转基因方法证明,Hk的野生型拷贝足以恢复正常睡眠。此外,我们表明,短睡眠的Hk突变品系存在记忆缺陷,而携带较弱的Hk次等位基因的果蝇睡眠正常且记忆正常。通过比较六个短睡眠的Sh品系和两个正常睡眠的品系,我们还发现只有减少睡眠的等位基因也会损害记忆。这些数据确定了一个维持正常睡眠所必需的基因Hk,并提供了短睡眠与记忆不佳相关的遗传学证据。

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