Inactivation of the Tuberomammillary Nucleus by GABAA Receptor Agonist Promotes Slow Wave Sleep in Freely Moving Rats and Histamine-Treated Rats
Inactivation of the Tuberomammillary Nucleus by GABAA Receptor Agonist Promotes Slow Wave Sleep in Freely Moving Rats and Histamine-Treated Rats
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DOI：
10.1007/s11064-017-2247-3
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发表时间：
2017-04
影响因子：
4.4
通讯作者：
Jun-Fan Xie;K. Fan;Can Wang;P. Xie;Min Hou;Le Xin;Guangjun Cui;Lin-Xin Wang;Yu-Feng Shao;Yi-ping Hou
中科院分区：
文献类型：
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作者：
Jun-Fan Xie;K. Fan;Can Wang;P. Xie;Min Hou;Le Xin;Guangjun Cui;Lin-Xin Wang;Yu-Feng Shao;Yi-ping Hou
一个突出的假说“触发器开关”模型预测，结节乳头核（TMN）中的组胺能（HAergic）神经元是上行唤醒系统的重要组成部分，主要被来自腹外侧视前核的 GABA 灭活，从而允许睡眠的出现和维持。然而，哪种睡眠状态以及 TMN GABA 能失活引起的脑电图活动带尚不清楚。在这项研究中，分别将蝇蕈醇（一种 GABAA 受体激动剂）双侧显微注射到自由活动大鼠和 HA 预处理大鼠的 TMN 中后，研究了睡眠-觉醒状态和皮质脑电图功率谱密度的变化。在黑暗时期，以 0.25 和 0.50 μg/侧剂量注入 TMN 中的蝇蕈醇可剂量依赖性地增加慢波睡眠 (SWS)，同时皮层 EEG δ (0.5–4 Hz) 和纺锤体 (8.2–12 Hz) 活动增加。与此同时，清醒状态和脑电图β（12.2-30Hz）活动显着下降，而反常睡眠和脑电图θ（4.2-8Hz）活动没有变化。蝇蕈醇诱导的 SWS 增加是因为 SWS 发作持续时间延长，而不是发作次数增加。 HA（0.125 μg/侧）在光照期间治疗 2 小时后给予蝇蕈醇（0.50 μg/侧）可将 HA 诱导的觉醒和 EEG beta 2 (20.2–30 Hz) 活性逆转为 SWS 和 EEG delta 活性。这些结果表明，自由活动的大鼠和HA处理的大鼠中TMN的GABA能失活促进了SWS并减慢了皮质脑电图的活动，这表明TMN中GABAA受体的潜在功能是抑制警惕性唤醒。
A prominent hypothesis, the “flip–flop switch” model, predicts that histaminergic (HAergic) neurons in the tuberomammillary nucleus (TMN), an important component of the ascending arousal system, are inactivated by GABA mainly from the ventrolateral preoptic nucleus to allow the appearance and maintenance of sleep. However, which sleep state and the band of EEG activity induced by GABAergic inactivation of the TMN are unclear. In this study, alterations of sleep-wake states and cortical EEG power spectral density were investigated following muscimol, a GABAA-receptor agonist, microinjected bilaterally into the TMN in freely moving rats and HA pretreated rats, respectively. Muscimol dosed at 0.25 and 0.50 μg/side into the TMN during dark period dose-dependently increased slow wave sleep (SWS) accompanied by an increase in cortical EEG delta (0.5–4 Hz) and spindle (8.2–12 Hz) activities. In the meanwhile, wakefulness and EEG beta (12.2–30 Hz) activity were decreased significantly, while paradoxical sleep and EEG theta (4.2–8 Hz) activity were not changed. The increase of muscimol-induced SWS was because of prolonged SWS bout duration and not to an increased bout number. Muscimol (0.50 μg/side) administration 2 h after HA (0.125 μg/side) treatment during light period reversed the HA-induced wakefulness and EEG beta 2 (20.2–30 Hz) activity into SWS and EEG delta activity. These results demonstrate that the GABAergic inactivation of the TMN in freely moving rats and HA-treated rats promotes SWS and slow activity of cortical EEG, suggesting that the potential function of the GABAAreceptor in the TMN is to dampen vigilant arousal.