A novel circadian output circuit linking sensory input to sleep/wake states

睡眠对于神经系统的正常功能至关重要，因此对于包括人类和果蝇在内的许多生物的正常行为也至关重要。我们入睡的时间通常被认为是由两个过程调控的。首先是内部计时器——生物钟。第二，测量我们疲劳程度的稳态器。这两个过程在很大程度上是内在的，但显而易见的事实是，我们的外部环境对我们的睡眠模式有深远的影响。促觉醒药物、人造光或不舒服的温度都会延迟或扰乱我们的睡眠，而低质量的睡眠与代谢和精神疾病有关。在非人类物种中，何时入睡是一个关键的决定，因为进食和交配暂停，生物体更容易受到捕食者的攻击。同样，环境信号必须被生物体感知，这些信号以某种方式传递到大脑的睡眠调节区域。更清楚地了解这一过程是如何在神经回路水平上发生的，这对于提高我们对包括人类在内的各种物种的睡眠是如何调节的理解至关重要。我们选择了果蝇——黑腹果蝇来研究这个问题。我们最近的研究表明，通过温度感应神经元向生物钟网络的一个子集DN1p神经元发送信号，雄性果蝇在早晨的高温下会延长清醒时间，DN1p神经元在早晨的高温下会促进清醒。我们现在确定了DN1p神经元下游的一种新的输出电路，它介导了这种效应。我们发现DN1p神经元投射到一个叫做前视结节（AOTU）的大脑区域。我们提供的数据显示，AOTU含有促进睡眠的神经元，这些神经元受到DN1p神经元的抑制。我们建议进行实验来详细描述该电路并确定其他下游连接。通过这些实验，我们的目标是发现果蝇的昼夜节律网络如何与果蝇大脑中的唤醒/睡眠促进中心联系在一起，以及这些回路的活动如何被环境刺激改变。

Sleep is essential for normal nervous system function, and thus normal behaviour, in a wide range of organisms, including species as divergent as humans and fruit flies. When we fall asleep is generally thought to be regulated by two processes. Firstly, an internal timekeeper - the circadian clock. Secondly, a homeostat that measures our level of tiredness. These two processes are largely internal, yet it is an obvious truth that our external environment has a profound impact on our sleep patterns. Pro-arousal drugs, artificial light or uncomfortable temperatures all delay or disrupt our sleep, and poor quality sleep has been linked to both metabolic and psychiatric disease. In non-human species, when to fall asleep is a critical decision, since eating and mating are paused and the organism becomes more vulnerable to predation. Here again, environmental cues must be sensed by an organism, and these cues somehow transmitted to sleep-regulatory regions of the brain. A clearer understanding of how this process occurs at the circuit level is critical to advance our understanding of how sleep is modulated in a variety of species, including humans. We have chosen the fruit fly, Drosophila melanogaster, to investigate this issue. We recently showed that high temperatures in the morning prolong wakefulness in male Drosophila via temperature-sensing neurons signalling to a subset of the circadian clock network called DN1p neurons, which are wake-promoting in the morning at high temperatures. We now identify a novel output circuit downstream of DN1p neurons that mediates this effect. We find that DN1p neurons project to a brain region called the Anterior Optic Tubercle (AOTU). We present data showing that the AOTU contains sleep-promoting neurons that are inhibited by DN1p neurons. We propose experiments to characterise this circuit in detail and to identify additional downstream connections. Through these experiments, we aim to discover how the circadian network in Drosophila is linked to wake/sleep-promoting centres in the fly brain, and how the activity of these circuits is altered by environmental stimuli.