Williams J A, Vincent S R, Reiner P B
Kinsmen Laboratory of Neurological Research, Department of Psychiatry, Graduate Program in Neuroscience, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.
J Neurosci. 1997 Jan 1;17(1):420-7. doi: 10.1523/JNEUROSCI.17-01-00420.1997.
Since its discovery as a putative neurotransmitter in the CNS, several functional roles have been suggested for nitric oxide (NO). However, few studies have investigated the role of NO in natural physiology. Because NO synthase (NOS) has been localized in regions believed to be important for attention and arousal, we hypothesized that NO production would be state-dependent. To test this hypothesis, we used in vivo microdialysis, coupled with the hemoglobin-trapping technique, to monitor extracellular NO concentrations in rat thalamus during wake, slow-wave sleep (SWS), and rapid eye movement (REM) sleep. The thalamus is known to receive a massive innervation from the NOS/cholinergic neurons in the mesopontine brainstem, which have been suggested to play a key role in EEG desynchronized states. To test whether thalamic NO output was sensitive to neuronal-dependent changes in the mesopontine brainstem, we measured thalamic NO concentration in response to electrical stimulation in the laterodorsal tegmentum (LDT) of anesthetized rats. Finally, the calcium dependence of NO release was tested by local depolarization with a high potassium dialysate or by addition of a calcium chelator. The results showed that (1) extracellular NO concentrations in the thalamus were high during wake and REM sleep and significantly lower during SWS, (2) thalamic NO release increased in response to LDT stimulation in both a site-specific and tetrodotoxin (TTX)-dependent manner, and (3) NO production was calcium-dependent. These data suggest that thalamic NO production may play a role in arousal.
自从一氧化氮（NO）在中枢神经系统中被发现是一种假定的神经递质以来，人们已经提出了它的几种功能作用。然而，很少有研究调查NO在自然生理中的作用。由于一氧化氮合酶（NOS）已定位在被认为对注意力和觉醒很重要的区域，我们假设NO的产生将取决于状态。为了验证这一假设，我们使用体内微透析结合血红蛋白捕获技术，监测大鼠丘脑在清醒、慢波睡眠（SWS）和快速眼动（REM）睡眠期间的细胞外NO浓度。已知丘脑接受来自中脑桥脑NOS/胆碱能神经元的大量神经支配，这些神经元被认为在脑电图去同步化状态中起关键作用。为了测试丘脑NO输出是否对中脑桥脑神经元依赖性变化敏感，我们测量了麻醉大鼠外侧背侧被盖区（LDT）电刺激后丘脑的NO浓度。最后，通过用高钾透析液进行局部去极化或添加钙螯合剂来测试NO释放的钙依赖性。结果表明：（1）丘脑的细胞外NO浓度在清醒和REM睡眠期间较高，在SWS期间显著较低；（2）丘脑NO释放以位点特异性和河豚毒素（TTX）依赖性方式对LDT刺激增加；（3）NO产生是钙依赖性的。这些数据表明丘脑NO的产生可能在觉醒中起作用。
