Kubin L, Kimura H, Tojima H, Davies R O, Pack A I
Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104.
Brain Res. 1993 May 21;611(2):300-12. doi: 10.1016/0006-8993(93)90517-q.
The depression of upper airway motor activity that develops during the rapid eye movement (REM) stage of sleep is a major factor allowing upper airway obstructions to occur in patients with sleep apnea syndrome. Microinjections of carbachol, a cholinergic agonist, into the dorsal pontine tegmentum of chronically instrumented cats produce REM sleep. In acutely decerebrate cats, carbachol induces postural atonia, eye movements and a depression of the motor output to respiratory pump and upper airway muscles. In lumbar motoneurons, the depression of activity is due to a glycinergic inhibition that has the same characteristics during natural REM sleep in chronic cats and carbachol-induced atonia in decerebrate cats (Neurophysiology, 57 (1987) 1118-1129). The mechanisms that lead to the suppression of upper airway motoneuronal activity during REM sleep are unknown. In this study, we assessed whether the depression of hypoglossal (XII) nerve activity induced by pontine carbachol injections is caused by inhibitory amino acids acting within the XII nucleus. In decerebrate, paralyzed and artificially ventilated cats, we recorded the activities of both XII nerves (genioglossal branches), one phrenic and a cervical motor branch (to monitor postural activity). Postural atonia and respiratory depression were induced by pontine carbachol injections. The inhibitory amino acid receptor antagonists, strychnine (glycine receptors) or bicuculline (GABAA receptors), were injected (100-250 nl; 1.0-2.5 mM) into one XII nucleus (the other served as control) in an attempt to reduce or abolish the depression subsequently induced by pontine carbachol. Prior to the carbachol injections, both antagonists caused similar elevations of XII nerve activity on the treated side (30-40%). However, following carbachol, the XII nerve activity on the treated side was depressed to about 25% of the (pre-antagonist and pre-carbachol) control level, whereas the depression on the untreated side was slightly greater, to 10-15% of the control. Additional injections of antagonists during the carbachol-induced depression produced no further increase in nerve activity. This minor effect of the antagonists on the carbachol-induced depression of XII nerve activity was in contrast to the marked disinhibitory effects that both antagonists had on the XII nerve response to electrical stimulation of the lingual nerve. The latter was used as a control for the ability of strychnine and bicuculline to exert disinhibitory effects within the XII nucleus. Thus, there is little, if any, contribution of these inhibitory amino acids to the depression of XII motoneurons during the carbachol-induced, REM sleep-like postural and respiratory depression; mechanisms other than fast synaptic inhibition must be involved.
睡眠快速眼动（REM）阶段出现的上气道运动活动抑制是睡眠呼吸暂停综合征患者发生上气道阻塞的一个主要因素。向长期植入仪器的猫的脑桥背侧被盖区微量注射胆碱能激动剂卡巴胆碱可产生REM睡眠。在急性去大脑猫中，卡巴胆碱可诱发姿势性肌张力缺失、眼球运动以及呼吸泵和上气道肌肉运动输出的抑制。在腰段运动神经元中，活动抑制是由于甘氨酸能抑制引起的，这种抑制在慢性猫的自然REM睡眠和去大脑猫中卡巴胆碱诱发的肌张力缺失过程中具有相同的特征（《神经生理学》，57卷（1987年）1118 - 1129页）。导致REM睡眠期间上气道运动神经元活动受抑制的机制尚不清楚。在本研究中，我们评估了脑桥注射卡巴胆碱所诱发的舌下神经（XII）活动抑制是否由XII核内起作用的抑制性氨基酸引起。在去大脑、麻痹并进行人工通气的猫中，我们记录了双侧XII神经（颏舌肌分支）、一侧膈神经和一条颈运动神经分支的活动（以监测姿势活动）。脑桥注射卡巴胆碱可诱发姿势性肌张力缺失和呼吸抑制。将抑制性氨基酸受体拮抗剂士的宁（甘氨酸受体）或荷包牡丹碱（GABAA受体）（100 - 250 nl；1.0 - 2.5 mM）注射到一侧XII核内（另一侧作为对照），试图减轻或消除随后由脑桥卡巴胆碱诱发的抑制。在注射卡巴胆碱之前，两种拮抗剂均使处理侧的XII神经活动有相似程度的升高（30 - 40%）。然而，注射卡巴胆碱后，处理侧的XII神经活动被抑制至（拮抗剂和卡巴胆碱注射前）对照水平的约25%，而未处理侧的抑制程度略大，为对照的10 - 15%。在卡巴胆碱诱发的抑制过程中额外注射拮抗剂并未使神经活动进一步增加。拮抗剂对卡巴胆碱诱发的XII神经活动抑制的这种轻微作用与它们对XII神经对舌神经电刺激反应的显著去抑制作用形成对比。后者被用作士的宁和荷包牡丹碱在XII核内发挥去抑制作用能力的对照。因此，在卡巴胆碱诱发的、类似REM睡眠的姿势和呼吸抑制过程中，这些抑制性氨基酸对上舌下运动神经元的抑制作用很小，若有作用的话；必定涉及快速突触抑制以外的机制。
