Role of inhibitory amino acids in control of hypoglossal motor outflow to genioglossus muscle in naturally sleeping rats
Role of inhibitory amino acids in control of hypoglossal motor outflow to genioglossus muscle in naturally sleeping rats
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DOI：
10.1113/jphysiol.2003.052357
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发表时间：
2003-11-01
影响因子：
5.5
通讯作者：
Horner, RL
中科院分区：
文献类型：
--
作者：
Morrison, JL;Sood, S;Horner, RL
舌下神经运动核支配舌头的颏舌肌（GG），该肌肉有助于维持有效呼吸的开放气道。然而，快速眼动（REM）睡眠招募了强大的神经机制，即使在强反射刺激（如高碳酸血症）期间也可以消除GG活动，这种影响可能使人类容易出现与睡眠相关的呼吸问题。我们已经建立了一个动物模型，在自由行为的大鼠体内使用微透析长期操纵舌下神经运动核的神经传递。本研究验证了以下假设：舌下神经运动核的甘氨酸受体拮抗剂，无论是单独使用还是与GABA（A）受体拮抗剂联合使用，都将防止在室内空气和CO2刺激呼吸期间自然REM睡眠中GG活性受到抑制。在大鼠体内植入脑电图和颈肌电极记录睡眠-觉醒状态，植入GG和膈肌电极记录呼吸肌状态。将微透析探针植入舌下神经运动核，在室内空气和CO2刺激的呼吸过程中灌注人工脑脊液（ACSF）和士的宁（甘氨酸受体拮抗剂，0.1 mM）单独或与荷包牡丹碱（GABA（A）拮抗剂，0.1 mM）组合。与ACSF对照组相比，在室内空气中，舌下神经运动核的甘氨酸受体拮抗剂增加了排尿相关的GG活性（P = 0.010），但不增加高碳酸血症（P = 0.221）。士的宁在室内空气中的这种刺激作用不依赖于当时的睡眠-觉醒状态（P = 0.625），表明去除了非特异性背景抑制性甘氨酸能音调。然而，在没有GG肌肉阶段性抽搐的REM睡眠期，GG活动保持最小，无论ACSF或士的宁是否位于舌下运动核或吸入的气体是室内空气或7%CO2，来自非REM（NREM）睡眠的GG抑制> 85%。虽然在这些REM睡眠期GG活性最小，但士的宁后GG活性有一个小但可测量的增加（P <0.05）。在没有GG抽搐的REM睡眠期，在舌下神经运动核的甘氨酸和GABA（A）受体联合拮抗作用下，GG活性也是最小的，并有效地被消除。我们的结论是，这些数据在自由行为的大鼠证实，抑制性甘氨酸和GABA（A）受体机制存在于舌下运动核和紧张性活动，但这种抑制机制只作出了很小的贡献，在自然REM睡眠期间观察到的GG活动和反射反应的显着抑制。
The hypoglossal motor nucleus innervates the genioglossus (GG) muscle of the tongue, a muscle that helps maintain an open airway for effective breathing. Rapid-eye-movement (REM) sleep, however, recruits powerful neural mechanisms that can abolish GG activity even during strong reflex stimulation such as by hypercapnia, effects that can predispose to sleep-related breathing problems in humans. We have developed an animal model to chronically manipulate neurotransmission at the hypoglossal motor nucleus using in vivo microdialysis in freely behaving rats. This study tests the hypothesis that glycine receptor antagonism at the hypoglossal motor nucleus, either alone or in combination with GABA(A) receptor antagonism, will prevent suppression of GG activity in natural REM sleep during room air and CO2-stimulated breathing. Rats were implanted with electroencephalogram and neck muscle electrodes to record sleep-wake states, and GG and diaphragm electrodes for respiratory muscle recording. Microdialysis probes were implanted into the hypoglossal motor nucleus for perfusion of artificial cerebrospinal fluid (ACSF) and strychnine (glycine receptor antagonist, 0.1 mM) either alone or combined with bicuculline (GABA(A) antagonist, 0.1 mm) during room air and CO2-stimulated breathing. Compared to ACSF controls, glycine receptor antagonism at the hypoglossal motor nucleus increased respiratory-related GG activity in room air (P = 0.010) but not hypercapnia (P = 0.221). This stimulating effect of strychnine in room air did not depend on the prevailing sleep-wake state (P = 0.625) indicating removal of a non-specific background inhibitory glycinergic tone. Nevertheless, GG activity remained minimal in those REM sleep periods without phasic twitches in GG muscle, with GG suppression from non-REM (NREM) sleep being > 85% whether ACSF or strychnine was at the hypoglossal motor nucleus or the inspired gas was room air or 7% CO2. While GG activity was minimal in these REM sleep periods, there was a small but measurable increase in GG activity after strychnine (P < 0.05). GG activity was also minimal, and effectively abolished, in the REM sleep periods without GG twitches with combined glycine and GABA(A) receptor antagonism at the hypoglossal motor nucleus. We conclude that these data in freely behaving rats confirm that inhibitory glycine and GABA(A) receptor mechanisms are present at the hypoglossal motor nucleus and are tonically active, but that such inhibitory mechanisms make only a small contribution to the marked suppression of GG activity and reflex responses observed in periods of natural REM sleep.