Light activates output from evening neurons and inhibits output from morning neurons in the Drosophila circadian clock.

Light activates output from evening neurons and inhibits output from morning neurons in the Drosophila circadian clock.
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DOI:
10.1371/journal.pbio.0050315
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发表时间:
2007-11
期刊:
影响因子:
9.8
通讯作者:
Rouyer F
Rouyer F
中科院分区:
生物学1区
文献类型:
--
作者:
Picot M;Cusumano P;Klarsfeld A;Ueda R;Rouyer F

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动物的生物钟是基于多个振荡器,它们的相互作用允许每天控制复杂的行为。果蝇的大脑包含一个控制休息-活动节律的生物钟,并依赖于不同的PERIOD(PER)表达神经元。两个不同的振荡器已在功能上的特点,在光暗周期。表达色素分散因子(PDF)的外侧神经元(LN)驱动早晨的活动,而PDF阴性的LN是晚上活动所必需的。在恒定黑暗条件下,几条证据表明LN晨振子(LN-MO)驱动活动节律,而LN晚振子(LN-EO)不驱动活动节律。由于突变体缺乏的功能性CYPTOCHROME(CRY),而不是野生型苍蝇,是有节奏的恒定光,我们分析了转基因苍蝇表达PER或CRY的LN-MO或LN-EO。我们发现,在恒定的光照条件下,减少CRY功能,LN晚上振荡驱动器强大的活动节奏,而LN上午振荡器没有。值得注意的是,光通过抑制LN-MO行为输出和激活LN-EO行为输出起作用。最后,我们表明,PDF信号是不需要强大的活动节奏,在恒定的光,而不是在恒定的黑暗中的要求,进一步支持在光的存在下,早晨细胞的行为的微小贡献。因此,我们建议昼夜周期交替激活果蝇晚上和早上侧神经元的行为输出。生物体已经进化出生物钟,可以预测其环境的日常变化。它们的时钟机制完全是内源性的,但可以通过外部线索重置。(光是最有效的线索。)果蝇(Drosophila)大脑的昼夜神经元网络通过视觉系统和专用的感光分子隐花色素感知光线。苍蝇表现出双峰运动活动模式,在黎明和黄昏时,在光暗条件下达到峰值。这些早晨和晚上的活动是由苍蝇大脑中两个不同的神经元时钟控制的。通过使用隐花色素途径缺陷的果蝇,我们发现了光在昼夜节律系统中的意想不到的作用。除了使两个振荡器与太阳时同步外,光还控制它们的行为输出。早晨的振子可以在持续黑暗中周期性地唤醒苍蝇,但在持续光照下却不能,而晚上的振子可以在持续光照下做同样的事情,但在持续黑暗中却不能。这表明,在振荡器之间存在一个依赖于光的开关,似乎需要视觉系统。这种机制可能有助于更好地区分黎明和黄昏时苍蝇的活动期,并可能帮助动物适应白天长度的季节性变化。在果蝇中,光不仅将生物钟重置为太阳时,而且还使一个振荡器发出信号,而另一个振荡器发出信号。
Animal circadian clocks are based on multiple oscillators whose interactions allow the daily control of complex behaviors. The Drosophila brain contains a circadian clock that controls rest–activity rhythms and relies upon different groups of PERIOD (PER)–expressing neurons. Two distinct oscillators have been functionally characterized under light-dark cycles. Lateral neurons (LNs) that express the pigment-dispersing factor (PDF) drive morning activity, whereas PDF-negative LNs are required for the evening activity. In constant darkness, several lines of evidence indicate that the LN morning oscillator (LN-MO) drives the activity rhythms, whereas the LN evening oscillator (LN-EO) does not. Since mutants devoid of functional CRYPTOCHROME (CRY), as opposed to wild-type flies, are rhythmic in constant light, we analyzed transgenic flies expressing PER or CRY in the LN-MO or LN-EO. We show that, under constant light conditions and reduced CRY function, the LN evening oscillator drives robust activity rhythms, whereas the LN morning oscillator does not. Remarkably, light acts by inhibiting the LN-MO behavioral output and activating the LN-EO behavioral output. Finally, we show that PDF signaling is not required for robust activity rhythms in constant light as opposed to its requirement in constant darkness, further supporting the minor contribution of the morning cells to the behavior in the presence of light. We therefore propose that day–night cycles alternatively activate behavioral outputs of the Drosophila evening and morning lateral neurons. Living organisms have evolved circadian clocks that anticipate daily changes in their environment. Their clockwork is fully endogenous, but can be reset by external cues. (Light is the most efficient cue.) The circadian neuronal network of the fruit fly (Drosophila) brain perceives light through the visual system and a dedicated photoreceptor molecule, cryptochrome. Flies exhibit a bimodal locomotor activity pattern that peaks at dawn and dusk in light–dark conditions. These morning and evening activity bouts are controlled by two distinct neuronal clocks in the fly brain. By using flies with a deficient cryptochrome pathway, we have uncovered an unexpected role for light in the circadian system. In addition to synchronizing the two oscillators to solar time, light also controls their behavioral output. The morning oscillator can periodically rouse the fly when in constant darkness, but not in constant light, whereas the evening oscillator can do the same in constant light, but not in constant darkness. This suggests the existence of a light-dependent switch between oscillators that appears to require the visual system. Such a mechanism likely contributes to better separate the active periods of the fly at dawn and dusk, and may help the animal to adapt to seasonal changes in day length. In fruit flies, light not only resets the circadian clock to solar time, but also enables the signaling from one oscillator while disabling the signaling from the other.
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