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

一种新颖的昼夜节律输出电路，将感觉输入与睡眠/唤醒状态联系起来

基本信息

批准号：
BB/R02281X/1
负责人：
James Jepson
金额：
$ 50.24万
依托单位：
University College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2018
资助国家：
英国
起止时间：
2018 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FR02281X%2F1
关键词：
novel circadian output circuit linking

项目摘要

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.

睡眠对于许多生物体（包括人类和果蝇等不同物种）的正常神经系统功能以及正常行为至关重要。我们入睡的时间通常被认为是由两个过程调节的。首先，一个内部计时器-生物钟。第二，一个衡量我们疲劳程度的自我平衡器。这两个过程在很大程度上是内在的，但我们的外部环境对我们的睡眠模式有着深远的影响，这是一个显而易见的事实。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，而睡眠质量差与代谢和精神疾病都有关。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，生物体变得更容易受到捕食。同样，生物体必须能够感知环境信号，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如何在电路层面发生，对于促进我们了解包括人类在内的各种物种的睡眠是如何调节的至关重要。我们选择果蝇，黑腹果蝇，来研究这个问题。我们最近发现，早上的高温通过温度感应神经元向称为DN 1 p神经元的昼夜节律钟网络的子集发出信号，延长了雄性果蝇的觉醒，DN 1 p神经元在早上高温下促进觉醒。我们现在确定了一个新的输出电路下游的DN 1 p神经元介导的这种效果。我们发现DN 1 p神经元投射到一个称为前视神经节（AOTU）的大脑区域。我们提供的数据表明，AOTU包含促进睡眠的神经元，这些神经元受到DN 1 p神经元的抑制。我们提出的实验，详细说明这个电路，并确定额外的下游连接。通过这些实验，我们的目标是发现果蝇的昼夜节律网络是如何与果蝇大脑中的唤醒/睡眠促进中心联系在一起的，以及这些回路的活动是如何被环境刺激改变的。