A medullary circuit controlling REM sleep

控制快速眼动睡眠的髓质回路

• 批准号: 10459228
• 负责人: Amanda Schott
• 金额: $ 4.6万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10459228
• 关键词: Address; Area; Attenuated; Axon; Behavioral; Brain; Brain Stem; Calcium; Cell Nucleus; Cells; Cognitive; Corticotropin-Releasing Hormone; Corticotropin-Releasing Hormone Receptors; Data; Dorsal; Dreams; EKG P Wave; Electrodes; Electroencephalography; Electrophysiology (science); Emotional; Event; Fiber; Frequencies; Generations; Glutamate Receptor; Glutamates; Hippocampus (Brain); Histologic; Human; Image; In Situ Hybridization; Knowledge; Label; Measurable; Measures; Mediating; Memory; Mental Processes; Modeling; Mus; Neurons; Neuropeptides; Neurotransmitters; Pathway interactions; Pharmacology; Phase; Play; Pontine structure; Population; Presynaptic Terminals; Probability; Process; REM Sleep; Research; Role; Site; Sleep; Sleep Stages; Slice; Testing; Theta Rhythm; Viral; Work; cell type; cognitive function; cognitive process; density; emotion regulation; experimental study; in vivo; insight; memory consolidation; neural circuit; novel; optogenetics; patch clamp; postsynaptic; response; sleep regulation

PROJECT SUMMARY Rapid eye movement (REM) sleep is a distinct brain state known for its association with vivid dreaming in humans, though it is also crucial for other cognitive functions such as memory consolidation and emotional processing. REM sleep is punctuated by short bursts of brain-wide electrical activity called ‘phasic events’, which can be measured as spike-like field potentials (P-waves) in the pons and as transient ‘theta bursts’ in the hippocampal EEG. A major knowledge gap in the field of REM sleep research lies in the identification of the neural circuits underlying i) REM sleep initiation, and ii) generation of phasic events within REM sleep. My early experiments in the Weber lab have suggested that a genetically distinct, heretofore unstudied population of neurons in the dorsomedial medulla (dmM) expressing corticotropin releasing hormone (CRH) could be important for both of these processes. I found that these novel dmM CRH+ neurons are selectively active during REM sleep, and that their activity is correlated with phasic hippocampal theta bursts. Importantly, optogenetic stimulation of the dmM CRH+ population promotes REM sleep in the mouse, suggesting that these neurons are functionally involved in controlling one or more features of REM sleep. Viral tracing experiments revealed CRH+ axons in the subcoeruleus area of the pons, which is the site of P-wave generation, as well as the nucleus incertus, a pontine region involved in the brainstem generation of the hippocampal theta rhythm. Given this preliminary data, I hypothesize that dmM CRH+ neurons are important for regulating i) REM sleep initiation, and ii) phasic events within REM sleep, via downstream projections to the pons. Aim 1 of my proposal will determine whether dmM CRH+ neurons promote REM sleep through interactions with the nucleus incertus, and whether these behavioral effects are mediated by the CRH neuropeptide itself. Aim 2 will test whether dmM CRH+ neurons are directly involved in generating pontine P- waves during REM sleep. Overall, these studies will rigorously interrogate the role of a novel pontomedullary circuit in REM sleep control, and elucidate the mechanisms by which the brainstem contributes to cognitive processing during this unique sleep stage.

项目摘要 快速眼动（REM）睡眠是一种独特的大脑状态，因其与生动的梦境有关而闻名， 虽然它对其他认知功能也至关重要，如记忆巩固和情感 处理.快速眼动睡眠期间会出现短暂的全脑电活动，称为“阶段性事件”， 其可以测量为脑桥中的尖峰样场电位（P波）和脑桥中的瞬时“θ波群”。 海马脑电图快速眼动睡眠研究领域的一个主要知识缺口在于确定 i）REM睡眠启动和ii）REM睡眠内阶段性事件产生的神经回路。我 韦伯实验室的早期实验表明，一个遗传上独特的，迄今尚未研究的种群， 在表达促肾上腺皮质激素释放激素（CRH）的背内侧髓质（dmM）神经元中， 对这两个过程都很重要。我发现这些新的dmM CRH+神经元选择性地激活 在REM睡眠期间，它们的活动与阶段性海马θ波爆发相关。重要的是， DMM CRH+群体的光遗传学刺激促进小鼠的REM睡眠，表明 这些神经元在功能上参与控制REM睡眠的一个或多个特征。病毒追踪 实验显示，在脑桥的蓝斑下区域，即P波的位置，存在CRH+轴突 在脑干的产生，以及涉及的脑桥区域，在神经元的脑干产生， 海马θ节律根据这些初步数据，我假设dmM CRH+神经元是重要的， 用于调节i）REM睡眠启动，和ii）REM睡眠内的阶段性事件，通过下游投射到 脑桥我的建议的目标1将确定dmM CRH+神经元是否通过以下方式促进REM睡眠： 与未定核的相互作用，以及这些行为效应是否由CRH介导 神经肽本身。目的2将测试dmM CRH+神经元是否直接参与产生脑桥P- 快速眼动睡眠时的脑电波总的来说，这些研究将严格询问一个新的桥脑延髓的作用， 回路在REM睡眠控制，并阐明机制，脑干有助于认知 在这个独特的睡眠阶段。