Sleep state-dependent functions of pontine waves

脑桥波的睡眠状态依赖性功能

• 批准号: MR/Y004051/1
• 负责人: Shuzo Sakata
• 金额: $ 75.05万
• 依托单位: University of Strathclyde
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY004051%2F1
• 关键词: Sleep; state; dependent; functions; pontine

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.

睡眠是必不可少的。睡眠不足与各种脑部疾病有关，如抑郁症、痴呆症、其他神经退行性疾病以及精神疾病。睡眠可以通过电生理特征来确定，并分为两种主要的睡眠状态：快速眼动（REM）睡眠和非快速眼动（NREM）睡眠。每个睡眠阶段都有一组独特的脑电波。例如，在非快速眼动睡眠期间，可以看到δ波或慢波活动。在快速眼动睡眠期间，可以看到θ波。除了出现在脑电图（EEG）上的脑电波外，人们还知道脑桥会产生一种突出的亚秒脑电波，称为“脑桥波”或p波。最近，我们的小组建立了一种实验方法来监测小鼠模型的p波。我们发现，在非快速眼动和快速眼动睡眠期间都可以观察到p波，并且p波与海马产生的脑电波相耦合。众所周知，海马体对学习和记忆至关重要，因此在本项目中，我们将通过实验验证p波在记忆巩固中发挥作用的假设。为此，我们将进行三个主要实验：首先，我们将研究是否可以通过跨大脑多个区域的神经元激活来实现p波和海马波之间的功能耦合，这些区域建立了桥脑桥和海马之间的通信。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叫做乙酰胆碱的神经递质，并向海马体提供输入，以及p波后乙酰胆碱的水平是否增加，以及乙酰胆碱的这种增加是否会阻止海马体产生另一种脑电波。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的活动。这个项目的结果将阐明脑桥中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，这些结果将为识别大脑疾病的新标志物和开发新的治疗方法提供机会。