Dopamine is a regulator of arousal in the fruit fly
Dopamine is a regulator of arousal in the fruit fly
复制标题
DOI：
10.1523/jneurosci.2048-05.2005
复制
发表时间：
2005-08-10
影响因子：
5.3
通讯作者：
Jackson, FR
中科院分区：
文献类型：
--
作者：
Kume, K;Kume, S;Jackson, FR
已知睡眠和觉醒受体内平衡和昼夜节律过程的调节，但其潜在的分子机制尚不清楚。据报道，果蝇的休息/活动周期与哺乳动物的睡眠/觉醒周期具有共同的特征，预计苍蝇遗传模型的使用将促进对睡眠和觉醒的分子理解。在这里，我们报告的果蝇休息/活性突变体称为富明（fmn）的表型特征。我们发现，fmn突变体有异常高水平的活动和减少休息（睡眠）;遗传图谱，分子分析和表型救援实验表明，这些表型的结果从果蝇多巴胺转运蛋白基因突变。与rest表型一致，fmn突变体表现出对机械刺激的敏感性增强，激活后唤醒时间延长，表明唤醒阈值降低。引人注目的是，fmn突变体没有表现出明显的反弹，在响应休息剥夺是典型的野生型苍蝇，也没有显示减少寿命。这些结果为多巴胺能信号在昆虫觉醒调节中的重要作用提供了直接证据。
Sleep and arousal are known to be regulated by both homeostatic and circadian processes, but the underlying molecular mechanisms are not well understood. It has been reported that the Drosophila rest/activity cycle has features in common with the mammalian sleep/wake cycle, and it is expected that use of the fly genetic model will facilitate a molecular understanding of sleep and arousal. Here, we report the phenotypic characterization of a Drosophila rest/activity mutant known as fumin (fmn). We show that fmn mutants have abnormally high levels of activity and reduced rest (sleep); genetic mapping, molecular analyses, and phenotypic rescue experiments demonstrate that these phenotypes result from mutation of the Drosophila dopamine transporter gene. Consistent with the rest phenotype, fmn mutants show enhanced sensitivity to mechanical stimuli and a prolonged arousal once active, indicating a decreased arousal threshold. Strikingly, fmn mutants do not show significant rebound in response to rest deprivation as is typical for wild-type flies, nor do they show decreased life span. These results provide direct evidence that dopaminergic signaling has a critical function in the regulation of insect arousal.