Membrane electrical excitability is necessary for the free-running larval Drosophila circadian clock
Membrane electrical excitability is necessary for the free-running larval Drosophila circadian clock
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DOI：
10.1002/neu.20053
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发表时间：
2005-01-01
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影响因子：
--
通讯作者：
Holmes, TC
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作者：
Nitabach, MN;Sheeba, V;Holmes, TC
果蝇幼虫和成年起搏神经元都表达自由运行的周期振荡（PER）和无时间（TIM）蛋白，构成细胞自主昼夜节律分子钟的核心。尽管成人和幼虫的分子振荡器之间的相似之处，成人和幼虫的起搏器神经回路的复杂性和组织，以及在昼夜节律的行为表现有很大的不同。我们以前已经表明，成年果蝇昼夜节律起搏神经元的电沉默通过靶向表达开放整流或内向整流K+通道停止自由运行的昼夜节律分子钟的振荡。这表明，起搏神经元的神经元电活动是必不可少的成人细胞内时钟的正常功能。在目前的研究中，我们表明，在恒定的黑暗中，自由运行的幼虫起搏器时钟就像它们产生的成年起搏神经元一样，需要膜电活动才能振荡。与自由运行的时钟相反，电沉默的幼虫起搏神经元的分子时钟在昼夜（光暗）条件下继续振荡。由靶向K+通道表达引起的自由运行时钟的这种特定中断可能反映了幼虫和成体神经元共同的特定细胞自主时钟膜反馈回路，并且不是由于阻断起搏器突触输出或起搏器神经元形态的中断。(C)2004 Wiley Periodicals，Inc.
Drosophila larvae and adult pacemaker neurons both express free-running oscillations of period (PER) and timeless (TIM) proteins that constitute the core of the cell-autonomous circadian molecular clock. Despite similarities between the adult and larval molecular oscillators, adults and larvae differ substantially in the complexity and organization of their pacemaker neural circuits, as well as in behavioral manifestations of circadian rhythmicity. We have shown previously that electrical silencing of adult Drosophila circadian pacemaker neurons through targeted expression of either an open rectifier or inward rectifier K+ channel stops the free-running oscillations of the circadian molecular clock. This indicates that neuronal electrical activity in the pacemaker neurons is essential to the normal function of the adult intracellular clock. In the current study, we show that in constant darkness the free-running larval pacemaker clock-like that of the adult pacemaker neurons they give rise to-requires membrane electrical activity to oscillate. In contrast to the free-running clock, the molecular clock of electrically silenced larval pacemaker neurons continues to oscillate in diurnal (light-dark) conditions. This specific disruption of the free-running clock caused by targeted K+ channel expression likely reflects a specific cell-autonomous clock-membrane feedback loop that is common to both larval and adult neurons, and is not due to blocking pacemaker synaptic outputs or disruption of pacemaker neuronal morphology. (C) 2004 Wiley Periodicals, Inc.