Leonard T O, Lydic R
Department of Anesthesia, Pennsylvania State University College of Medicine, Hershey 17033, USA.
J Neurosci. 1997 Jan 15;17(2):774-85. doi: 10.1523/JNEUROSCI.17-02-00774.1997.
Pontine cholinergic neurotransmission is known to play a key role in the regulation of rapid eye movement (REM) sleep and to contribute to state-dependent respiratory depression. Nitric oxide (NO) has been shown to alter the release of acetylcholine (ACh) in a number of brain regions, and previous studies indicate that NO may participate in the modulation of sleep/wake states. The present investigation tested the hypothesis that inhibition of NO synthase (NOS) within the medial pontine reticular formation (mPRF) of the unanesthetized cat would decrease ACh release, inhibit REM sleep, and prevent cholinergically mediated respiratory depression. Local NOS inhibition by microdialysis delivery of N(G)-nitro-L-arginine (NLA) significantly reduced ACh release in the cholinergic cell body region of the pedunculopontine tegmental nucleus and in the cholinoceptive mPRF. A second series of experiments demonstrated that mPRF microinjection of NLA significantly reduced the amount of REM sleep and the REM sleep-like state caused by mPRF injection of the acetylcholinesterase inhibitor neostigmine. Duration but not frequency of REM sleep epochs was significantly decreased by mPRF NLA administration. Injection of NLA into the mPRF before neostigmine injection also blocked the ability of neostigmine to decrease respiratory rate during the REM sleep-like state. Taken together, these findings suggest that mPRF NO contributes to the modulation of ACh release, REM sleep, and breathing.
已知脑桥胆碱能神经传递在快速眼动(REM)睡眠调节中起关键作用,并导致与睡眠状态相关的呼吸抑制。一氧化氮(NO)已被证明可改变许多脑区乙酰胆碱(ACh)的释放,先前的研究表明NO可能参与睡眠/觉醒状态的调节。本研究检验了以下假设:在未麻醉猫的脑桥内侧网状结构(mPRF)内抑制一氧化氮合酶(NOS)会减少ACh释放、抑制REM睡眠并预防胆碱能介导的呼吸抑制。通过微透析给予N(G)-硝基-L-精氨酸(NLA)进行局部NOS抑制,可显著降低脚桥被盖核胆碱能细胞体区域和胆碱能感受性mPRF中的ACh释放。第二系列实验表明,向mPRF微量注射NLA可显著减少REM睡眠量以及由mPRF注射乙酰胆碱酯酶抑制剂新斯的明所引起的REM睡眠样状态。mPRF给予NLA可显著降低REM睡眠时段的持续时间,但不影响其频率。在新斯的明注射前向mPRF注射NLA,也可阻断新斯的明在REM睡眠样状态下降低呼吸频率的能力。综上所述,这些发现表明mPRF中的NO有助于调节ACh释放、REM睡眠和呼吸。