Andretic Rozi, van Swinderen Bruno, Greenspan Ralph J
The Neuroscience Institute, San Diego, California 92121, USA.
Curr Biol. 2005 Jul 12;15(13):1165-75. doi: 10.1016/j.cub.2005.05.025.
Arousal levels in the brain set thresholds for behavior, from simple to complex. The mechanistic underpinnings of the various phenomena comprising arousal, however, are still poorly understood. Drosophila behaviors have been studied that span different levels of arousal, from sleep to visual perception to psychostimulant responses.
We have investigated neurobiological mechanisms of arousal in the Drosophila brain by a combined behavioral, genetic, pharmacological, and electrophysiological approach. Administration of methamphetamine (METH) suppresses sleep and promotes active wakefulness, whereas an inhibitor of dopamine synthesis promotes sleep. METH affects courtship behavior by increasing sexual arousal while decreasing successful sexual performance. Electrophysiological recordings from the medial protocerebrum of wild-type flies showed that METH ingestion has rapid and detrimental effects on a brain response associated with perception of visual stimuli. Recordings in genetically manipulated animals show that dopaminergic transmission is required for these responses and that visual-processing deficits caused by attenuated dopaminergic transmission can be rescued by METH.
We show that changes in dopamine levels differentially affect arousal for behaviors of varying complexity. Complex behaviors, such as visual perception, degenerate when dopamine levels are either too high or too low, in accordance with the inverted-U hypothesis of dopamine action in the mammalian brain. Simpler behaviors, such as sleep and locomotion, show graded responses that follow changes in dopamine level.
大脑中的觉醒水平为行为设定阈值，从简单行为到复杂行为皆是如此。然而，构成觉醒的各种现象的机制基础仍知之甚少。果蝇的行为已得到研究，其行为涵盖了从睡眠到视觉感知再到精神刺激反应等不同程度的觉醒。
我们通过行为学、遗传学、药理学和电生理学相结合的方法，研究了果蝇大脑中觉醒的神经生物学机制。给予甲基苯丙胺（METH）会抑制睡眠并促进主动觉醒，而多巴胺合成抑制剂则会促进睡眠。METH通过增加性唤起同时降低成功的性行为表现来影响求偶行为。对野生型果蝇中脑前叶的电生理记录表明，摄入METH会对与视觉刺激感知相关的大脑反应产生快速且有害的影响。对基因操作动物的记录显示，这些反应需要多巴胺能传递，并且由多巴胺能传递减弱引起的视觉处理缺陷可以通过METH得到挽救。
我们表明，多巴胺水平的变化对不同复杂程度行为的觉醒有不同影响。根据哺乳动物大脑中多巴胺作用的倒U型假说，当多巴胺水平过高或过低时，诸如视觉感知等复杂行为会退化。诸如睡眠和运动等较简单的行为则表现出随多巴胺水平变化的分级反应。
