Sensory processing during sleep in Drosophila melanogaster

大多数动物在睡眠时会进入一种意识改变的状态，使它们与周围的世界分离，从而允许长时间的不受干扰的休息。然而，与此同时，他们还必须保持一定程度的意识，以便在受到相关刺激的挑战时醒来。通过降低神经元水平的反应阈值，可以过滤掉大部分定量的刺激（如爆炸声的响度、灯光的亮度），但目前还不清楚睡眠中的大脑如何定性地辨别刺激（如单词的含义、愤怒的语调）。在20世纪60年代首次发现，睡眠中的人类会对自己的名字做出反应，后来在老鼠，猫和灵长类动物中进行了概念上类似的观察。为了在一个遗传模型中探索这一现象的神经基础，我们转向醋蝇，黑腹果蝇。果蝇的睡眠概括了哺乳动物睡眠的大多数行为特征，包括对唤醒阈值的常规调节。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，我们建立了一个机器人机器，能够选择性地探测单个苍蝇，具有相同机械强度但不同气味显着性的空气喷流，并使用这种新的实验范式，我们能够证明苍蝇有能力在睡眠期间识别刺激的定性显着性，类似于人类所做的。我们提出的研究建立在这些初步发现的基础上，并有望进一步扩展它们，从而开创了一个新的研究领域：在一个遗传上适合的动物模型中研究睡眠期间的信息感觉处理。特别是，我们想更好地了解调节这种现象的神经元是什么。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？当其他神经元必须“睡眠”而没有反应时，它们怎么能负担得起呢？这项研究对更大的神经科学界很重要，因为它提供了在不同的意识状态（清醒和睡眠）下大脑如何解码感觉输入的信息。它对睡眠社区也很重要，因为它解决了睡眠最令人困惑的方面之一：它的成本。我们仍然不知道睡眠的功能是什么，但无论是什么，它都需要动物与外部世界断开联系，这可能会带来非常高的危险。这项研究可以揭示神经元如何实现这种断开，以及其中一些神经元如何以及为什么能够逃脱这种断开。

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.