Sleep state-dependent functions of pontine waves

睡眠是必不可少的。睡眠不佳与各种大脑疾病有关，如抑郁症、痴呆症和其他神经退行性疾病以及精神障碍。睡眠可由电生理信号决定，分为两种主要睡眠状态：快速眼动睡眠(REM)和非快速眼动睡眠(NREM)。每个睡眠阶段都有一组独特的脑电波。例如，在NREM睡眠期间，可以看到三角洲波或慢波活动。在REM睡眠中，可以看到theta波。除了出现在脑电图(EEG)中的这种脑波外，众所周知，桥脑还会产生一种显著的亚秒级脑波，称为“脑桥波”或P波。最近，我们团队建立了一种在小鼠模型中监测P波的实验方法。我们发现，在NREM和REM睡眠期间都可以观察到P波，而且P波与海马区产生的脑波是耦合的。由于众所周知，海马体对学习和记忆至关重要，在本项目中，我们将通过实验验证P波在记忆巩固中起作用的假设。为此，我们将进行三个主要实验：首先，我们将检验P波和海马波之间的这种功能耦合是否可以通过跨脑桥和海马区之间建立联系的多个脑区的神经元激活来实现。其次，我们将确定P波是否可以激活一组特定的神经元，这些神经元产生一种名为乙酰胆碱的神经递质，并向海马区提供输入，以及P波之后乙酰胆碱水平是否会增加，以及这种乙酰胆碱水平的增加是否会阻止海马区产生另一种脑波。最后，我们将确定人工控制P波是否会影响记忆，以及这种影响是否取决于睡眠阶段。为了实现这些目标，我们将结合各种最先进的技术来监测和控制神经元活动。该项目的结果将阐明脑桥睡眠相关活动的重要性，不仅对睡眠调节，而且对认知功能，如记忆。最终，这些结果将提供一个机会来识别大脑疾病的新标记物，并为它们开发新的治疗方法。

Sleep is essential. Poor sleep is associated with various brain disorders, such as depression, dementia, and other neurodegenerative diseases as well as psychiatric disorders. Sleep can be determined by electrophysiological signatures and classified into two major sleep states: rapid eye movement (REM) sleep and non-REM (NREM) sleep. Each sleep stage is characterised by a unique set of brain waves. For example, during NREM sleep, delta waves or slow wave activity can be seen. During REM sleep, theta waves can be seen. In addition to such brain waves that appear in electroencephalography (EEG), the pons is also known to generate a prominent subsecond brain wave, called "pontine waves" or P-waves. Recently our group has established an experimental approach to monitor P-waves in a mouse model. We found that P-waves can be observed during both NREM and REM sleep and that P-waves are coupled with brain waves generated in the hippocampus. Because the hippocampus is well known to be critical for learning and memory, in this project, we will experimentally test the hypothesis that P-waves play a role in memory consolidation.To this end, we will conduct three major experiments:Firstly, we will examine if the such functional coupling between P-waves and hippocampal waves can be realized through neuronal activation across multiple brain regions which establish communications between the pons and the hippocampus. Secondly, we will determine if P-waves can activate a specific set of neurons that produce a neurotransmitter, called acetylcholine, and provide inputs to the hippocampus, and if the level of acetylcholine is increased after P-waves, and if the such increase in acetylcholine prohibits the generation of another brain wave in the hippocampus. Finally, we will determine if artificial control of P-waves can affect memory and if such effects depend on sleep stages. To achieve these goals, we will combine various state-of-the-art technologies to monitor and control neuronal activity. The outcomes of this project will shed light on the importance of sleep-related activity in the pons for not just sleep regulation, but also cognitive functions, such as memory. Ultimately, these outcomes will provide an opportunity to identify novel markers of brain disorders and develop a novel treatment for them.