Sleep regulation by neuron-astrocyte interactions

睡眠对我们的健康生活是必不可少的。睡眠异常与神经退行性疾病和神经精神疾病有关。更好地理解睡眠控制的机制很重要。睡眠表现出两种主要睡眠状态的周期，称为快速眼动睡眠(REM)和非快速眼动睡眠(NREM)。尽管过去几十年来有过研究，但与非快速眼动睡眠相比，快速眼动睡眠是如何控制的还不太清楚。快速眼动睡眠的特点是做梦生动，眼球快速运动，肌肉张力和其他身体内稳特征。快速眼动睡眠控制回路广泛分布于脑干和下丘脑，涉及一系列神经递质和神经肽。在这些脑区中，一个被称为背外侧下核(SLD)的脑干核与REM睡眠诱导和肌肉张力有关。然而，SLD是如何控制REM睡眠的还不清楚。在这个项目中，我们将重点研究SLD中的非神经细胞，称为星形胶质细胞。目前的一项理论预测，星形胶质细胞的细胞内钙活动在清醒时增加，在非快速眼动睡眠时减少。因此，星形胶质细胞扮演着“清醒整合者”的角色，有助于睡眠的动态平衡。然而，我们最近发现SLD星形胶质细胞在NREM睡眠期间钙信号增加。基于这一意想不到的发现，我们假设SLD星形胶质细胞在REM睡眠控制中发挥作用。通过结合小鼠体内的各种技术，我们将专门研究SLD星形胶质细胞中钙信号是如何控制的，以及SLD星形胶质细胞中钙信号增加的功能后果是什么。该项目的成果将有助于更好地了解睡眠控制的机制，并最终有助于开发新的睡眠药物。

Sleep is essential for our healthy lives. Abnormalities in sleep are associated with neurodegenerative and neuropsychiatric diseases. It is important to better understand the mechanism underpinning sleep control.Sleep exhibits cycles of two major sleep states, called rapid eye movement (REM) sleep and non-REM (NREM) sleep. Despite previous studies over the past decades, compared to NREM sleep, it is less clear how REM sleep is controlled. REM sleep is characterized by vivid dreaming, rapid eye movement, muscle atonia and other body homeostatic signatures. REM sleep-controlling circuits are widespread throughout the brainstem and the hypothalamus and involve a range of neurotransmitters and neuropeptides. Of these brain areas, a brainstem nucleus, called the sublaterodorsal nucleus (SLD) has been implicated in REM sleep induction and muscle atonia. However, it is unclear how the SLD controls REM sleep. In this project, we will focus on non-neuronal cells in the SLD, called astrocytes. A current theory predicts that intracellular calcium activity in astrocytes increases during wakefulness and decreases during NREM sleep. Thereby astrocytes act as a 'wakefulness integrator' to contribute to sleep homeostasis. However, we recently discovered that calcium signals increase during NREM sleep in SLD astrocytes. Based on this unexpected finding, we hypothesize that SLD astrocytes play a role in REM sleep control.By combining various in vivo technologies in mice, we will specifically investigate how calcium signals in SLD astrocytes are controlled and what is the functional consequence of the increased calcium signals in SLD astrocytes. The outcome of this project will contribute to a better understanding of the mechanisms of sleep control and ultimately to the development of novel sleep medicine.