An AP2 Transcription Factor Is Required for a Sleep-Active Neuron to Induce Sleep-like Quiescence in C. elegans
An AP2 Transcription Factor Is Required for a Sleep-Active Neuron to Induce Sleep-like Quiescence in C. elegans
复制标题
DOI：
10.1016/j.cub.2013.09.028
复制
发表时间：
2013-11-18
期刊：
影响因子：
9.2
通讯作者：
Bringmann, Henrik
中科院分区：
文献类型：
--
作者：
Turek, Michal;Lewandrowski, Ines;Bringmann, Henrik
背景：睡眠是一种基本行为，存在于所有有神经系统的动物身上。神经活动被认为控制睡眠，但人们对睡眠背后的神经回路的身份和功能知之甚少。Lethargus是线虫幼虫具有睡眠特性的发育调节期。结果：我们研究了线虫幼虫的睡眠行为，发现它需要一个高度保守的AP2转录因子aptf-1，它只在头部的5个中间神经元中强烈表达。在这些神经元之一的GABA能神经元RIS中，APTF-1的表达需要静止。RIS在从觉醒行为向睡眠行为的转变过程中被强烈而尖锐地激活。Aptf-1表达神经元的光遗传激活以aptf-1依赖的方式异位诱导急性行为静止。RIS消融后静息时间显著减少。然而，RIS依赖的静止不需要GABA，而需要神经肽信号。结论：RIS是一个睡眠活跃、促进睡眠的神经元，需要aptf-1通过神经肽信号诱导睡眠样行为。在脊椎动物的大脑中也发现了促进睡眠的GABA能-肽能神经元，这表明在脊椎动物的睡眠和无脊椎动物的睡眠行为之间存在共同的电路原理。
Background: Sleep is an essential behavior that is found in all animals that have a nervous system. Neural activity is thought to control sleep, but little is known about the identity and the function of neural circuits underlying sleep. Lethargus is a developmentally regulated period of behavioral quiescence in C. elegans larvae that has sleep-like properties.Results: We studied sleep-like behavior in C. elegans larvae and found that it requires a highly conserved AP2 transcription factor, aptf-1, which was expressed strongly in only five interneurons in the head. Expression of aptf-1 in one of these neurons, the GABAergic neuron RIS, was required for quiescence. RIS was strongly and acutely activated at the transition from wake-like to sleep-like behavior. Optogenetic activation of aptf-1-expressing neurons ectopically induced acute behavioral quiescence in an aptf-1-dependent manner. RIS ablation caused a dramatic reduction of quiescence. RIS-dependent quiescence, however, does not require GABA but requires neuropeptide signaling.Conclusions: We conclude that RIS acts as a sleep-active, sleep-promoting neuron that requires aptf-1 to induce sleep-like behavior through neuropeptide signaling. Sleep-promoting GABAergic-peptidergic neurons have also been identified in vertebrate brains, suggesting that common circuit principles exist between sleep in vertebrates and sleep-like behavior in invertebrates.