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从遗传学、结构到功能:探索果蝇的睡眠。

From genetics to structure to function: exploring sleep in Drosophila.

机构信息

Department of Psychiatry, University of Wisconsin, 6001 Research Park Blvd.Madison, WI 53719, USA.

出版信息

Int Rev Neurobiol. 2011;99:213-44. doi: 10.1016/B978-0-12-387003-2.00009-4.

DOI:10.1016/B978-0-12-387003-2.00009-4
PMID:21906542
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3172676/
Abstract

Sleep consists of quiescent periods with reduced responsiveness to external stimuli. Despite being maladaptive in that when asleep, animals are less able to respond to dangerous stimuli; sleep behavior is conserved in all animal species studied to date. Thus, sleep must be performing at least one fundamental, conserved function that is necessary, and/or whose benefits outweigh its maladaptive consequences. Currently, there is no consensus on what that function might be. Over the last 10 years, multiple groups have started to characterize the molecular mechanisms and brain structures necessary for normal sleep in Drosophila melanogaster. These researchers are exploiting genetic tools developed in Drosophila over the past century to identify and manipulate gene expression. Forward genetic screens can identify molecular components in complex biological systems and once identified, these genes can be manipulated within specific brain areas to determine which neuronal groups are important to initiate and maintain sleep. Screening for mutations and brain regions necessary for normal sleep has revealed that several genes that affect sleep are involved in synaptic plasticity and have preferential expression in the mushroom bodies (MBs). Moreover, altering MB neuronal activity alters sleep. Previous genetic screens found that the same genes enriched in MB are necessary for learning and memory. Increasing evidence in mammals, including humans, points to a beneficial role for sleep in synaptic plasticity, learning and memory. Thus, results from both flies and mammals suggest a strong link between sleep need and wake plasticity.

摘要

睡眠由对外界刺激反应性降低的静止期组成。尽管睡眠在适应不良方面表现明显,因为动物在睡眠时对危险刺激的反应能力降低;但迄今为止,所有研究过的动物物种都保留了睡眠行为。因此,睡眠必须执行至少一种基本的、保守的功能,这种功能是必要的,和/或其益处超过了适应不良的后果。目前,对于这个功能可能是什么,还没有共识。在过去的 10 年中,多个研究小组已经开始描述在黑腹果蝇中正常睡眠所必需的分子机制和大脑结构。这些研究人员正在利用过去一个世纪在果蝇中开发的遗传工具来识别和操纵基因表达。正向遗传筛选可以在复杂的生物系统中识别分子成分,一旦确定,这些基因可以在特定的大脑区域中进行操作,以确定哪些神经元群体对于启动和维持睡眠很重要。筛选正常睡眠所必需的突变和大脑区域表明,一些影响睡眠的基因参与突触可塑性,并且在蘑菇体(MB)中优先表达。此外,改变 MB 神经元的活动会改变睡眠。以前的遗传筛选发现,在 MB 中富集的相同基因对于学习和记忆是必需的。包括人类在内的哺乳动物的越来越多的证据表明,睡眠对突触可塑性、学习和记忆有有益的作用。因此,来自果蝇和哺乳动物的结果都表明睡眠需求和清醒可塑性之间存在很强的联系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb1/3172676/9e45f844cc09/nihms317306f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb1/3172676/9e45f844cc09/nihms317306f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb1/3172676/9e45f844cc09/nihms317306f1.jpg

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