Nall Aleksandra H, Shakhmantsir Iryna, Cichewicz Karol, Birman Serge, Hirsh Jay, Sehgal Amita
Cell and Molecular Biology Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Biology, University of Virginia, Charlottesville, VA 22904, USA.
Sci Rep. 2016 Feb 12;6:20938. doi: 10.1038/srep20938.
Caffeine is the most widely-consumed psychoactive drug in the world, but our understanding of how caffeine affects our brains is relatively incomplete. Most studies focus on effects of caffeine on adenosine receptors, but there is evidence for other, more complex mechanisms. In the fruit fly Drosophila melanogaster, which shows a robust diurnal pattern of sleep/wake activity, caffeine reduces nighttime sleep behavior independently of the one known adenosine receptor. Here, we show that dopamine is required for the wake-promoting effect of caffeine in the fly, and that caffeine likely acts presynaptically to increase dopamine signaling. We identify a cluster of neurons, the paired anterior medial (PAM) cluster of dopaminergic neurons, as the ones relevant for the caffeine response. PAM neurons show increased activity following caffeine administration, and promote wake when activated. Also, inhibition of these neurons abrogates sleep suppression by caffeine. While previous studies have focused on adenosine-receptor mediated mechanisms for caffeine action, we have identified a role for dopaminergic neurons in the arousal-promoting effect of caffeine.
咖啡因是世界上消费最为广泛的精神活性药物，但我们对咖啡因如何影响大脑的了解相对不完整。大多数研究聚焦于咖啡因对腺苷受体的作用，但有证据表明还存在其他更复杂的机制。在具有强烈昼夜睡眠/觉醒活动模式的果蝇中，咖啡因可独立于已知的一种腺苷受体减少夜间睡眠行为。在此，我们表明多巴胺是咖啡因在果蝇中促进觉醒作用所必需的，并且咖啡因可能通过作用于突触前增加多巴胺信号传导。我们确定了一组神经元，即成对的前内侧（PAM）多巴胺能神经元簇，为与咖啡因反应相关的神经元。给予咖啡因后，PAM神经元的活动增加，激活时会促进觉醒。此外，抑制这些神经元可消除咖啡因对睡眠的抑制作用。虽然之前的研究聚焦于腺苷受体介导的咖啡因作用机制，但我们已经确定了多巴胺能神经元在咖啡因促进觉醒作用中的作用。
