视前谷氨酸能神经元对快速眼动和非快速眼动睡眠的调节。

IF 4.9 2区 医学 Q1 Medicine
Sleep Pub Date : 2025-09-09 DOI:10.1093/sleep/zsaf141
Alejandra Mondino, Amir Jadidian, Brandon A Toth, Viviane S Hambrecht-Wiedbusch, Leonor Floran-Garduno, Duan Li, A Kane York, Pablo Torterolo, Dinesh Pal, Christian R Burgess, George A Mashour, Giancarlo Vanini
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引用次数: 0

摘要

下丘脑的视前区是控制睡眠开始和睡眠稳态的关键。虽然传统上被认为是睡眠基因,但最近的研究发现了一组促进觉醒的视前谷氨酸能神经元。具体来说,我们之前的研究表明,化学发生刺激中外侧视前区(MLPO_VGLUT2)内的谷氨酸能神经元促进觉醒,破坏非快速眼动睡眠(nrem),并抑制快速眼动睡眠(REM)。最近的研究进一步支持了这一证据,研究表明视前谷氨酸能神经元在微觉醒期间被激活,从而在应激反应中分裂睡眠,光遗传刺激这些神经元促进微觉醒和觉醒。因此,虽然MLPO_VGLUT2的促醒功能是明确的,但其在睡眠稳态中的作用尚未得到评估。我们验证了MLPO_VGLUT2是清醒激活的假设,它们的激活将通过对唤醒促进系统的投射增加清醒并破坏睡眠稳态。利用纤维光度法,我们发现MLPO_VGLUT2在快速眼动、清醒和短暂觉醒期间高度活跃,在非快速眼动期间保持最低活性。化学发生刺激MLPO_VGLUT2抑制了rem的发生(与同时低温造成的rem断裂无关),并抑制了完全睡眠剥夺后的rem稳态反应。化学发生抑制MLPO_VGLUT2增加了rem时间(仅在光期),但不影响rem和nrem的稳态。顺行投影映射显示MLPO_VGLUT2支配中枢区域,促进觉醒和抑制rem。我们的结论是,MLPO_VGLUT2有效抑制rem,这些神经元的外源性(可能是病理性)激活可能通过直接或间接激活rem抑制机制破坏rem恢复。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Regulation of REM and NREM sleep by preoptic glutamatergic neurons.

The preoptic area of the hypothalamus is key for the control of sleep onset and sleep homeostasis. Although traditionally considered exclusively somnogenic, recent studies identified a group of preoptic glutamatergic neurons that promote wakefulness. Specifically, our previous investigations demonstrated that chemogenetic stimulation of glutamatergic neurons within the medial-lateral preoptic area (MLPO_VGLUT2) promotes wakefulness, fragments non-rapid eye movement sleep (NREMs), and suppresses REM sleep (REMs). This evidence is further supported by recent work showing that preoptic glutamatergic neurons are activated during microarousals that fragment sleep in response to stress, and optogenetic stimulation of these neurons promotes microarousals and wakefulness. Thus, while the wake-promoting function of MLPO_VGLUT2 is clear, their role in sleep homeostasis has not been assessed. We tested the hypothesis that MLPO_VGLUT2 are wake-active, and their activation will increase wakefulness and disrupt sleep homeostasis via projections to arousal-promoting systems. Using fiber photometry, we found that MLPO_VGLUT2 were highly active during REMs, wakefulness, and brief arousals, and remained minimally active during NREMs. Chemogenetic stimulation of MLPO_VGLUT2 inhibited REMs onset-independent of NREMs fragmentation produced by simultaneous hypothermia-and suppressed the REMs homeostatic response after total sleep deprivation. Chemogenetic inhibition of MLPO_VGLUT2 increased REMs time (during the light phase only) but did not influence REMs and NREMs homeostasis. Anterograde projection mapping revealed that MLPO_VGLUT2 innervates central regions that promote wakefulness and inhibit REMs. We conclude that MLPO_VGLUT2 powerfully suppresses REMs and that exogenous-and possibly pathologic-activation of these neurons disrupts REMs recovery, presumably by directly or indirectly activating REMs-inhibitory mechanisms.

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来源期刊
Sleep
Sleep Medicine-Neurology (clinical)
CiteScore
8.70
自引率
10.70%
发文量
0
期刊介绍: SLEEP® publishes findings from studies conducted at any level of analysis, including: Genes Molecules Cells Physiology Neural systems and circuits Behavior and cognition Self-report SLEEP® publishes articles that use a wide variety of scientific approaches and address a broad range of topics. These may include, but are not limited to: Basic and neuroscience studies of sleep and circadian mechanisms In vitro and animal models of sleep, circadian rhythms, and human disorders Pre-clinical human investigations, including the measurement and manipulation of sleep and circadian rhythms Studies in clinical or population samples. These may address factors influencing sleep and circadian rhythms (e.g., development and aging, and social and environmental influences) and relationships between sleep, circadian rhythms, health, and disease Clinical trials, epidemiology studies, implementation, and dissemination research.
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