Sleep regulation by neuron-astrocyte interactions

睡眠对我们的健康生活至关重要。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是很重要的。睡眠有两种主要的睡眠状态：快速眼动睡眠（REM）和非快速眼动睡眠（NREM）。尽管过去几十年的研究表明，与非快速眼动睡眠相比，快速眼动睡眠是如何被控制的还不太清楚。快速眼动睡眠的特点是做梦生动，眼球快速运动，肌肉松弛和其他身体稳态特征。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。在这些大脑区域中，有一个被称为嗅觉下核（SLD）的脑干核与快速眼动睡眠诱导和肌肉张力失调有关。然而，目前尚不清楚SLD是如何控制REM睡眠的。在这个项目中，我们将专注于SLD中的非神经元细胞，称为星形胶质细胞。目前的理论预测星形胶质细胞的细胞内钙活性在清醒时增加，在非快速眼动睡眠时减少。因此，星形胶质细胞充当“清醒整合者”，有助于睡眠稳态。然而，我们最近发现，在非快速眼动睡眠期间，SLD星形胶质细胞中的钙信号增加。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。通过在小鼠体内结合多种技术，我们将具体研究SLD星形胶质细胞钙信号是如何被控制的，以及SLD星形胶质细胞钙信号增加的功能后果。该项目的结果将有助于更好地理解睡眠控制的机制，并最终促进新型睡眠药物的发展。

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.