Department of Biology, New York University, 100 Washington Square East, New York, NY 10003, USA.
Curr Biol. 2012 Oct 23;22(20):1871-80. doi: 10.1016/j.cub.2012.07.070. Epub 2012 Aug 30.
Circadian (∼24 hr) rhythms offer one of the best examples of how gene expression is tied to behavior. Circadian pacemaker neurons contain molecular clocks that control 24 hr rhythms in gene expression that in turn regulate electrical activity rhythms to control behavior.
Here we demonstrate the inverse relationship: there are broad transcriptional changes in Drosophila clock neurons (LN(v)s) in response to altered electrical activity, including a large set of circadian genes. Hyperexciting LN(v)s creates a morning-like expression profile for many circadian genes while hyperpolarization leads to an evening-like transcriptional state. The electrical effects robustly persist in per(0) mutant LN(v)s but not in cyc(0) mutant LN(v)s, suggesting that neuronal activity interacts with the transcriptional activators of the core circadian clock. Bioinformatic and immunocytochemical analyses suggest that CREB family transcription factors link LN(v) electrical state to circadian gene expression.
The electrical state of a clock neuron can impose time of day to its transcriptional program. We propose that this acts as an internal zeitgeber to add robustness and precision to circadian behavioral rhythms.
昼夜节律(约 24 小时)为基因表达与行为之间的关系提供了最好的范例之一。昼夜节律起搏器神经元包含分子钟,控制着 24 小时基因表达的节律,进而调节电活动节律以控制行为。
在这里,我们证明了相反的关系:果蝇钟神经元(LN(v)s)的转录有广泛的变化,以响应电活动的改变,包括一大组昼夜节律基因。过度兴奋的 LN(v)s 使许多昼夜节律基因呈现出类似早晨的表达模式,而超极化则导致类似傍晚的转录状态。电效应在 per(0)突变体 LN(v)s 中稳健地持续存在,但在 cyc(0)突变体 LN(v)s 中不存在,这表明神经元活动与核心昼夜节律钟的转录激活因子相互作用。生物信息学和免疫细胞化学分析表明,CREB 家族转录因子将 LN(v)的电状态与昼夜节律基因表达联系起来。
时钟神经元的电状态可以为其转录程序施加时间。我们提出,这作为一个内部时间信号,为昼夜节律行为节律增加稳健性和精度。