Microdialysis perfusion of 5-HT into hypoglossal motor nucleus differentially modulates genioglossus activity across natural sleep-wake states in rats

Microdialysis perfusion of 5-HT into hypoglossal motor nucleus differentially modulates genioglossus activity across natural sleep-wake states in rats
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DOI:
10.1111/j.1469-7793.2001.0467f.x
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发表时间:
2001-04-15
影响因子:
5.5
通讯作者:
Horner, RL
Horner, RL
中科院分区:
医学1区
文献类型:
--
作者:
Jelev, A;Sood, S;Horner, RL

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1.5-羟色胺(5-羟色胺,5-羟色胺)兴奋舌下运动神经元(XII),提示5-羟色胺的退出可能是睡眠中膝舌肌(GG)活动减少的原因。然而,人体内全身应用5-羟色胺制剂对GG活性的影响有限。是否将5-羟色胺直接应用于第十二运动神经核会增加清醒或睡眠状态下的GG活性,这一点尚未得到测试。本研究的目的是建立一种新的自由行为动物模型,用于睡眠-觉醒状态下在体微透析XII运动核团,并验证5-羟色胺应用将增加GG活性的假说。18只大鼠植入脑电和颈肌电极以记录睡眠-觉醒状态,G、G和横隔膜电极用于记录呼吸肌。微透析探头植入XII运动核团,注入人工脑脊液或10 mM 5-羟色胺。GG活动的正常下降发生在清醒、非快速眼动(Non-REM)和患有ACSP的快速眼动睡眠(REM)(P<0.01)。与ACSF相比,5-羟色胺在所有睡眠-觉醒状态下都能显著激活GG(增加91-251%,P<0.015)。重要的是,只要使用5-羟色胺(3-5小时),5-羟色胺就会将睡眠中的GG活性增加到正常清醒水平。尽管有5-羟色胺的紧张性刺激,但与非REM睡眠相比,REM睡眠中出现了GG抑制和兴奋的时相。结果表明,睡眠-觉醒状态对12号运动核内5-羟色胺的GG反应有不同的调制作用。这种利用尾侧延髓体内微透析的动物模型将能够确定自然睡眠中潜在的咽部运动控制的神经机制。
1. Serotonin (5-hydroxytryptamine, 5-HT) excites hypoglossal (XII) motoneurons in reduced preparations, and it has been suggested that withdrawal of 5-HT may underlie reduced genioglossus (GG) muscle activity in sleep. However, systemic administration of 5-HT agents in humans has limited effects on GG activity. Whether 5-HT applied directly to the XII motor nucleus increases GG activity in an intact preparation either awake or asleep has not been tested.2. The aim of this study was to develop a novel freely behaving animal model for in vivo microdialysis of the XII motor nucleus across sleep-wake states, and test the hypothesis that 5-HT application will increase GG activity.3. Eighteen rats were implanted with electroencephalogram and neck muscle electrodes to record sleep-wake states, and G G; and diaphragm electrodes for respiratory muscle recording. Microdialysis probes were implanted into the XII motor nucleus and perfused with artificial cerebrospinal fluid (ACSF) or 10 mM 5-HT.4. Normal decreases in GG activity occurred from wakefulness to non-rapid eye movement (non-REM) and REM sleep with ACSP (P < 0.01). Compared to ACSF, 5-HT caused marked GG activation across all sleep-wake states (increases of 91-251%, P < 0.015). Importantly, 5-HT increased sleeping GG activity to normal waking levels for as long as 5-HT was applied (3-5 h). Despite tonic stimulation by 5-HT, periods of phasic GG suppression and excitation occurred in REM sleep compared with non-REM.5. The results show that sleep-wake states differentially modulate GG responses to 5-HT at the,XII motor nucleus. This animal model using in vivo microdialysis of the caudal medulla will enable the determination of neural mechanisms underlying pharyngeal motor control in natural sleep.