Sensory processing during sleep in Drosophila melanogaster

睡觉时，大多数动物进入一种意识改变的状态，使它们与周围的世界分离，从而获得长时间的不受干扰的休息。然而，与此同时，他们也必须保持一定程度的意识，以便在受到相关刺激时醒来。大多数是定量的刺激（例如，爆炸声的响度，灯光的亮度）可以通过降低神经元水平的反应阈值来过滤掉，但尚不清楚睡眠中的大脑如何能够定性地区分刺激（例如，一个词的意思，一种生气的语气）。20世纪60年代，人们首次发现，睡觉的人会对别人叫自己的名字做出反应。后来，在老鼠、猫和灵长类动物身上也进行了类似的观察。为了在一个基因可接受的模型中探索这种现象的神经元基础，我们转向了醋蝇，果蝇。果蝇的睡眠再现了哺乳动物睡眠的大部分行为特征，包括对觉醒阈值的刻板调节。人们普遍认为，睡眠中的苍蝇对机械刺激的反应会随着刺激的强度和动物的内部状态而变化，但睡眠中的苍蝇也能像人类一样定性地区分刺激吗？为了解决这个问题，我们建造了一个机器人机器，能够有选择地用相同机械强度但不同气味显著性的空气来探测单个苍蝇，使用这个新的实验范式，我们能够证明苍蝇有能力在睡眠中识别刺激的定性显著性，类似于人类的行为。我们提出的研究建立在这些初步发现的基础上，并承诺进一步扩展它们，从而开拓一个新的研究领域：在基因可调节的动物模型中研究睡眠期间信息的感觉处理。特别是，我们想更好地了解是什么神经元在调节这种现象。在大脑中充当哨兵并维持感知和解码外部感觉信息的能力的神经元是什么？当其他的神经元只能毫无反应地“睡觉”时，它们怎么能这样做呢？这项研究对更大的神经科学界来说很重要，因为它提供了在清醒和睡眠的不同意识状态下，大脑如何解码感觉输入的信息。这项研究对睡眠学界也很重要，因为它解决了睡眠最令人困惑的一个方面：睡眠的成本。我们仍然不知道睡眠的功能是什么，但不管它是什么，它要求动物以潜在的非常高的危险代价与外部世界断开联系。这项研究可以揭示神经元是如何实现这种分离的，以及其中一些神经元是如何以及为什么能够逃脱这种分离的。

When asleep, most animals enter a state of altered consciousness that detaches them from the surrounding world allowing for prolonged episodes of undisturbed rest. At the same time, however, they must also maintain some level of awareness necessary to wake up when challenged by relevant stimuli. Stimuli that are mostly quantitative (e.g. the loudness of a bang, the brightness of a light) can be filtered out by lowering the response threshold at the neuronal level, but it is unclear how a sleeping brain could discriminate stimuli qualitatively (e.g. the meaning of a word, an angry tone of voice). It was first shown in the 1960s that sleeping humans respond to the sound of their own names being called and conceptually similar observations were later made in rats, cats, and primates. To explore the neuronal underpinnings of this phenomenon in a genetically amenable model, we turned to the vinegar fly, Drosophila melanogaster. Sleep in flies recapitulates most of the behavioural characteristics of sleep in mammals, including a stereotypical modulation of arousal threshold. It has been widely established that the reaction of a sleeping fly to a mechanical stimulus varies with the intensity of the stimulus and the internal state of the animal, but can sleeping flies, like humans, discriminate stimuli qualitatively too? To address this question we built a robotic machine able to selectively probe single flies with air puffs of identical mechanical intensity but different odour saliency and using this new experimental paradigm we were able to prove that flies have the ability to recognise the qualitative saliency of a stimulus during sleep, similarly to what humans do. The research we are proposing builds on these preliminary findings and promises to extend them further thus pioneering a little new research field: the study of sensory processing of information during sleep in a genetically amenable animal model. In particular, we want to better understand what are the neurons that regulate this phenomenon. What are the neurons that act as sentinels in the brain and maintain the ability to perceive and decode external sensory information? How can they afford to do so while the rest of the other neurons must instead "sleep" unresponsive?This research is important for the larger neuroscientific community because it provides information on how a sensory input is decoded within the brain during different states of conscious awareness: wake and sleep. It is also important for the sleep community because it addresses one of the most puzzling aspects of sleep: its cost. We still do not know what is the function of sleep but whatever that is, it requires animals to disconnect from the external world at a potentially very high cost in terms of danger. This research can shed light on how neurons achieve this disconnect and how and why some of them actually manage to escape it.