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

From genetics to structure to function: exploring sleep in Drosophila.
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DOI:
10.1016/b978-0-12-387003-2.00009-4
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发表时间:
2011
影响因子:
--
通讯作者:
Cirelli, Chiara
Cirelli, Chiara
中科院分区:
医学3区
文献类型:
--
作者:
Bushey, Daniel;Cirelli, Chiara

文献摘要

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睡眠包括对外界刺激反应减弱的静止期。尽管在睡眠时,动物对危险刺激的反应能力较低,但睡眠行为在迄今为止研究的所有动物物种中都是保守的。因此,睡眠必须执行至少一个基本的,保守的功能是必要的,和/或其好处超过其适应不良的后果。目前,对这一职能可能是什么没有共识。在过去的10年里,多个研究小组已经开始研究果蝇正常睡眠所需的分子机制和大脑结构。这些研究人员正在利用过去世纪在果蝇中开发的遗传工具来识别和操纵基因表达。正向遗传筛选可以识别复杂生物系统中的分子成分,一旦识别出来,这些基因就可以在特定的大脑区域内进行操作,以确定哪些神经元群对启动和维持睡眠很重要。对正常睡眠所必需的突变和大脑区域的筛选揭示了影响睡眠的几个基因参与突触可塑性,并在蘑菇体(MB)中优先表达。此外,改变MB神经元活动也会改变睡眠。先前的基因筛选发现,富含MB的相同基因是学习和记忆所必需的。越来越多的证据表明,包括人类在内的哺乳动物的睡眠在突触可塑性、学习和记忆中发挥着有益的作用。因此,果蝇和哺乳动物的研究结果表明,睡眠需求和觉醒可塑性之间存在密切联系。
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 (MB). 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.