Department of Physiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
J Sleep Res. 2013 Dec;22(6):721-6. doi: 10.1111/jsr.12061. Epub 2013 May 24.
Cholinergic basal forebrain structures are implicated in cortical arousal and regulation of the sleep-wake cycle. Cholinergic neurones are innervated by noradrenergic terminals, noradrenaline excites them via alpha-1 receptors and microinjection of noradrenaline into the basal forebrain enhances wakefulness. However, it is not known to what extent the cholinergic versus non-cholinergic basal forebrain projection neurones contribute to the arousing effects of noradrenaline. To elucidate the roles of cholinergic basal forebrain structures we administered methoxamine, an alpha-1-adrenergic agonist into the basal forebrain, in intact animals and again after selective destruction of the basal forebrain cholinergic cells by 192 IgG-saporin. In eight male Han-Wistar rats implanted with electroencephalogram/electromyogram electrodes, a microdialysis probe targeted into the basal forebrain was perfused with artificial cerebrospinal fluid for 6 h on a baseline day, and with cerebrospinal fluid in the first and with methoxamine in the second 3-h period of the subsequent day. The sleep-wake activity was recorded for 24 h on both days. Saporin was then injected into the basal forebrain and 2 weeks later the same experimental schedule (with cerebrospinal fluid and methoxamine) was repeated. In the intact animals, methoxamine exhibited a robust arousing effect and non-rapid eye movement (NREM) and REM sleep was suppressed. Lesioning of the basal forebrain cholinergic neurones abolished almost completely the NREM sleep-suppressing effect of methoxamine, whereas the REM sleep-suppressing effect remained intact. Thus, the basal forebrain cholinergic neurones mediate, at least in part, cortical arousal and non-REM sleep-suppression, but they are not involved in the REM sleep-suppressing effects of noradrenaline.
胆碱能基底前脑结构参与皮质觉醒和睡眠-觉醒周期的调节。胆碱能神经元受去甲肾上腺素能末梢支配，去甲肾上腺素通过α-1 受体兴奋它们，并且将去甲肾上腺素微注射到基底前脑会增强觉醒。然而，尚不清楚基底前脑的胆碱能与非胆碱能投射神经元在去甲肾上腺素的唤醒作用中贡献的程度。为了阐明基底前脑结构的胆碱能作用，我们在完整动物中以及在基底前脑胆碱能细胞被 192 IgG 蓖麻毒素选择性破坏后，将甲氧胺（一种α-1 肾上腺素能激动剂）注入基底前脑。在 8 只雄性 Han-Wistar 大鼠中，植入脑电图/肌电图电极，将微透析探针靶向基底前脑，在基线日用人工脑脊液灌注 6 小时，然后在随后的第一天的前 3 小时用脑脊液，后 3 小时用甲氧胺。在两天内记录 24 小时的睡眠-觉醒活动。然后将蓖麻毒素注入基底前脑，两周后重复相同的实验方案（使用脑脊液和甲氧胺）。在完整动物中，甲氧胺表现出强大的唤醒作用，非快速眼动（NREM）和 REM 睡眠被抑制。基底前脑胆碱能神经元的损伤几乎完全消除了甲氧胺对 NREM 睡眠的抑制作用，而 REM 睡眠的抑制作用仍然存在。因此，基底前脑的胆碱能神经元至少部分介导皮质觉醒和非 REM 睡眠抑制，但它们不参与去甲肾上腺素的 REM 睡眠抑制作用。
