A medullary circuit controlling REM sleep

项目总结 快速眼动睡眠(REM)是一种独特的大脑状态，以其与生动的梦境有关而闻名。 人类，尽管它对其他认知功能也是至关重要的，如记忆巩固和情感 正在处理。在快速眼动睡眠中，整个大脑都会出现短时间的电活动，这种电活动被称为“时相事件”。 它可以在脑桥被测量为棘状场电位(P波)，在脑桥中被测量为瞬时的“theta爆发” 海马区脑电。快速眼动睡眠研究领域的一个主要知识空白在于确定 潜在的神经回路i)REM睡眠启动，以及ii)在REM睡眠内产生相事件。我的 韦伯实验室的早期实验表明，一个基因截然不同的、迄今未被研究的种群 在延髓背内侧(DMM)表达促肾上腺皮质激素释放激素(CRH)的神经元 对这两个过程都很重要。我发现这些新的DMM CRH+神经元是选择性激活的 在快速眼动睡眠期间，它们的活动与海马theta爆发的时相相关。重要的是 DMM CRH+群体的光遗传刺激促进了小鼠的REM睡眠，这表明 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 实验发现，CRH+轴突位于脑桥蓝斑下区域，也就是P波的位置 第四代，以及Incertus核，这是一个参与脑干生成的脑桥区域 海马塞塔节律。鉴于这些初步数据，我假设DMM CRH+神经元是重要的 用于调节i)REM睡眠启动，以及ii)REM睡眠内的阶段事件，通过下游投射到 庞斯。我提案的目标1将确定DMM CRH+神经元是否通过 与Incertus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。Aim 2将测试DMM CRH+神经元是否直接参与脑桥P- 快速眼动睡眠中的波。总体而言，这些研究将严格询问一个新的桥延髓的作用 REM睡眠控制中的回路，并阐明脑干促进认知的机制 在这个独特的睡眠阶段进行处理。

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.