Circuit control of REM sleep

快速眼动睡眠的电路控制

• 批准号: RGPIN-2018-06515
• 负责人: Peever, John
• 金额: $ 4.74万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=661826
• 关键词: Circuit; control; REM; sleep

Understanding how the brain controls REM sleep******REM sleep is one of the three fundamental behavioural states experienced by mammals, birds and reptiles (wakefulness and non-REM sleep are the other two). REM sleep is characterized by vivid dreaming, cortical activation and skeletal muscle paralysis, and is important for nervous system development, brain cell function, memory consolidation and certain forms of learning. Science magazine identified how and why we dream during REM sleep as being one of the 100 most important, but unanswered questions, in science. But, despite more than 6 decades of research it still remains unclear how the brain generates REM sleep. One reason for the limited progress in identifying how the brain controls REM sleep stems from the technical limitations associated with conventional science tools. However, new technologies called optogenetics and chemogenetics are now making it possible to study the brain circuits that turn REM sleep on and off. The goal of this NSERC research is to identify the core brain circuits that control REM sleep in mice using cutting-edge optogenetic and chemogenetic strategies. ******REM sleep is important for normal animal physiology, and is a unique behavioural state characterized by hippocampal theta activity (which is an important type of brain-wave that promotes learning) and skeletal muscle paralysis. However, the mechanisms that switch REM sleep on and off and that produce its defining features (theta activity and muscle atonia) remain poorly understood. The objectives of this proposal are to: ******1) Identify the core brain circuits that generate REM sleep. ***2) Determine which circuits function to terminate periods of REM sleep. ***3) Define the circuits that induce hippocampal theta activity and muscle atonia during REM sleep.******Our goal is to study the brain cells that control REM sleep using the latest and most precise tools in science, called optogenetics and chemogenetics. These tools are important for understanding how the brain controls REM sleep because they allow us to rapidly turn specific brain cells “on” and “off” so that their roles in producing REM sleep can be accurately determined. For example, if a particular type of brain cell is involved in producing REM sleep then switching it “off” should prevent REM sleep and switching in “on” should cause REM sleep. These experiments will therefore allow us to carefully study and identify how the cell circuits in a mouse's brain produce REM sleep. ******These experiments are important to biology and medicine because they will advance our understanding of how the brain controls REM sleep, which will allow biologists to better understand the natural functions of REM sleep and will allow clinicians to better understand and treat diseases like REM sleep behaviour disorder - a devastating neurodegenerative disease that in 80% of patients eventually leads to Parkinson's disease or dementia with Lewy bodies.

了解大脑如何控制快速眼动睡眠 * 快速眼动睡眠是哺乳动物、鸟类和爬行动物经历的三种基本行为状态之一（觉醒和非快速眼动睡眠是另外两种）。快速眼动睡眠的特征是生动的梦，皮层激活和骨骼肌麻痹，对神经系统发育，脑细胞功能，记忆巩固和某些形式的学习很重要。《科学》杂志将我们如何以及为什么在快速眼动睡眠期间做梦列为100个最重要但尚未解答的科学问题之一。但是，尽管经过60多年的研究，大脑如何产生快速眼动睡眠仍然不清楚。在确定大脑如何控制REM睡眠方面进展有限的一个原因是与传统科学工具相关的技术限制。然而，光遗传学和化学遗传学的新技术现在使研究快速眼动睡眠的开启和关闭的大脑回路成为可能。这项NSERC研究的目标是使用尖端的光遗传学和化学遗传学策略来确定控制小鼠REM睡眠的核心脑回路。** 快速眼动睡眠对正常的动物生理很重要，是一种独特的行为状态，其特征是海马体θ活动（这是一种重要的脑波，促进学习）和骨骼肌麻痹。然而，快速眼动睡眠的开关机制以及产生快速眼动睡眠特征（θ波活动和肌肉张力）的机制仍然知之甚少。这项建议的目标是：*1）识别产生快速眼动睡眠的核心大脑回路。*2）确定哪些回路起终止REM睡眠期的作用。*3）定义在REM睡眠期间诱导海马体theta活动和肌肉松弛的回路。**我们的目标是研究控制快速眼动睡眠的脑细胞，使用最新和最精确的科学工具，称为光遗传学和化学遗传学。这些工具对于理解大脑如何控制快速眼动睡眠非常重要，因为它们允许我们快速地“打开”和“关闭”特定的脑细胞，从而可以准确地确定它们在产生快速眼动睡眠中的作用。例如，如果一种特定类型的脑细胞参与了快速眼动睡眠的产生，那么将其关闭应该会阻止快速眼动睡眠，而将其打开应该会导致快速眼动睡眠。因此，这些实验将使我们能够仔细研究和识别老鼠大脑中的细胞回路如何产生REM睡眠。** 这些实验对生物学和医学很重要，因为它们将促进我们对大脑如何控制快速眼动睡眠的理解，这将使生物学家更好地了解REM睡眠的自然功能，并将使临床医生更好地了解和治疗REM睡眠行为障碍等疾病-一种破坏性的神经退行性疾病，80%的人最终导致帕金森病或路易体痴呆。