Cape E G, Manns I D, Alonso A, Beaudet A, Jones B E
Department of Neurology and Neurosurgery, McGill University, Montreal Neurological Institute, Montreal, Quebec, Canada H3A 2B4.
J Neurosci. 2000 Nov 15;20(22):8452-61. doi: 10.1523/JNEUROSCI.20-22-08452.2000.
Cholinergic basal forebrain neurons have long been thought to play an important role in cortical activation and behavioral state, yet the precise way in which they influence these processes has yet to be fully understood. Here, we have examined the effects on the electroencephalogram (EEG) and sleep-wake state of basal forebrain administration of neurotensin (NT), a neuropeptide that has been shown in vitro to potently and selectively modulate the cholinergic cells. Microinjection of (0.1-3.0 mm) NT into the basal forebrain of freely moving, naturally waking-sleeping rats produced a dose-dependent decrease in delta ( approximately 1-4 Hz) and increase in both theta ( approximately 4-9 Hz) and high-frequency gamma activity (30-60 Hz) across cortical, areas with no increase in the electromyogram. These EEG changes were accompanied by concomitant decreases in slow wave sleep (SWS) and transitional SWS (tSWS), increases in wake, and most remarkably, increases in paradoxical sleep (PS) and transitional PS (tPS), despite the virtual absence of SWS. The effects were attributed to direct action on cholinergic neurons as evidenced by selective internalization of a fluorescent ligand, Fluo-NT, in choline acetyltransferase (ChAT)-immunoreactive cells and stimulation by NT of bursting discharge in juxtacellularly recorded, Neurobiotin-labeled, ChAT-immunoreactive neurons. We conclude that NT-induced rhythmic bursting of cholinergic basal forebrain neurons stimulates rhythmic theta oscillations and gamma across the cerebral cortex. With the selective action of NT on the cholinergic cells, their bursting discharge promotes theta and gamma independent of motor activity and thereby also stimulates and enhances PS.
胆碱能基底前脑神经元长期以来一直被认为在皮层激活和行为状态中发挥重要作用，然而它们影响这些过程的确切方式尚未完全明了。在此，我们研究了神经降压素（NT）注入基底前脑对脑电图（EEG）和睡眠-觉醒状态的影响，NT是一种神经肽，已在体外实验中显示能有效且选择性地调节胆碱能细胞。将（0.1 - 3.0毫米）NT微量注射到自由活动、自然睡眠-觉醒的大鼠基底前脑，可使整个皮层区域的δ波（约1 - 4赫兹）剂量依赖性降低，θ波（约4 - 9赫兹）和高频γ波活动（30 - 60赫兹）增加，而肌电图无增加。这些EEG变化伴随着慢波睡眠（SWS）和过渡性慢波睡眠（tSWS）的减少、觉醒的增加，最显著的是，尽管几乎没有SWS，但异相睡眠（PS）和过渡性异相睡眠（tPS）增加。这些效应归因于对胆碱能神经元的直接作用，荧光配体Fluo-NT在胆碱乙酰转移酶（ChAT）免疫反应性细胞中的选择性内化以及NT对细胞旁记录的、Neurobiotin标记的、ChAT免疫反应性神经元爆发性放电的刺激证明了这一点。我们得出结论，NT诱导的胆碱能基底前脑神经元节律性爆发刺激了整个大脑皮层的节律性θ振荡和γ波。由于NT对胆碱能细胞的选择性作用，它们的爆发性放电促进了θ波和γ波，而与运动活动无关，从而也刺激并增强了PS。
