GABAergic regulation of the perifornical-lateral hypothalamic neurons during non-rapid eye movement sleep in rats.

GABAergic regulation of the perifornical-lateral hypothalamic neurons during non-rapid eye movement sleep in rats.
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DOI:
10.1016/j.neuroscience.2010.02.038
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发表时间:
2010-05-19
期刊:
影响因子:
3.3
通讯作者:
McGinty, D.
McGinty, D.
中科院分区:
医学3区
文献类型:
--
作者:
Alam, M. N.;Kumar, S.;Suntsova, N.;Bashir, T.;Szymusiak, R.;McGinty, D.

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下丘脑周围外侧区(PF-LHA)与行为唤醒的调节有关。 PF-LHA 主要包含在行为和皮层激活期间活跃且在非快速眼动 (nonNREM) 睡眠期间静止的神经元,即非快速眼动关闭神经元。一些体外和体内研究表明,PF-LHA 神经元,包括表达下丘脑分泌素的神经元,受到 GABA 能的控制。然而,GABA 在自发非快速眼动睡眠期间抑制 PF-LHA 神经元放电的作用尚未得到证实。我们记录了 PF-LHA 神经元的睡眠-觉醒放电曲线,并通过反向微透析将 GABAA 受体激动剂、蝇蕈醇(500nm、5μM 和 10μM)及其拮抗剂荷包牡丹碱(5μM、10μM 和 20μM)输送到记录的神经元附近,同时评估了局部 GABAA 受体激活和阻断对其觉醒和非快速眼动睡眠相关放电活动的贡献。蝇蕈醇剂量依赖性地减少 PF-LHA 神经元(包括非快速眼动关闭神经元)的放电。蝇蕈醇在非快速眼动睡眠期间引起的放电抑制明显弱于清醒时产生的抑制。在荷包牡丹碱存在的情况下,PF-LHA 神经元(包括非快速眼动关闭神经元)表现出放电增加,这是剂量依赖性的,并且与清醒时相比,在非快速眼动睡眠期间显着更高。这些结果表明,GABAA 受体介导的 GABA 能色调增加有助于抑制自发性非快速眼动睡眠期间的 PF-LHA 神经元,包括非快速眼动关闭神经元。
The perifornical-lateral hypothalamic area (PF-LHA) has been implicated in the regulation of behavioral arousal. The PF-LHA predominantly contains neurons that are active during behavioral and cortical activation and quiescent during non-rapid eye movement (nonNREM) sleep, i.e., are nonREM-off neurons. Some in vitro and in vivo studies indicate that PF-LHA neurons, including hypocretin-expressing neurons, are under GABAergic control. However, a role of GABA in suppressing the discharge of PF-LHA neurons during spontaneous nonREM sleep has not been confirmed. We recorded the sleep-wake discharge profiles of PF-LHA neurons and simultaneously assessed the contributions of local GABAA receptor activation and blockade on their wake- and nonREM sleep-related discharge activities by delivering GABAA receptor agonist, muscimol (500nm, 5μM, and 10μM) and its antagonist, bicuculline (5μM, 10μM, and 20μM), adjacent to the recorded neurons via reverse microdialysis. Muscimol dose-dependently decreased the discharge of PF-LHA neurons including nonREM-off neurons. Muscimol-induced suppression of discharge during nonREM sleep was significantly weaker than the suppression produced during waking. In the presence of bicuculline, PF-LHA neurons, including nonREM-off neurons, exhibited elevated discharge, which was dose-dependent and was significantly higher during nonREM sleep, compared to waking. These results suggest that GABAA receptor mediated increased GABAergic tone contributes to the suppression of PF-LHA neurons, including nonREM-off neurons, during spontaneous nonREM sleep.
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