Study on Neural and Humoral Control Mechanisms of REM Sleep

长期以来，人们认为脑干背外侧被盖核的胆碱能神经元在诱导和维持快速眼动睡眠中起重要作用。这些研究证实了这一点，在这些研究中，在未受过训练的动物中记录了胆碱能神经元的单个神经元活动，这些神经元重复睡眠和清醒；在我们使用大鼠进行的研究中，其特点是在体内鉴定了胆碱能神经元的spike活性，其spike结构比其他神经元更宽。因此，本研究旨在阐明哪些神经元驱动胆碱能神经元。所有实验均采用大鼠。首先，检查胆碱能神经元是否或如何对额叶皮质、视前区、下丘脑后乳状体、丘脑或海马的电刺激作出反应。最常见的是从下丘脑部位（视前区和乳状体）被正视驱赶。在视前区也获得了最常见的反相位反应。这些结果表明，下丘脑和脑干在控制睡眠和觉醒方面相互合作。然后，研究了胆碱能神经元对局部施加的递质的反应。所有的胆碱能神经元亚群，根据它们在睡眠和清醒时的行为分类，都被去甲肾上腺素抑制，这与猫的神经元不同。组胺有兴奋作用。下丘脑神经激素催乳素（Hypothalamic neurohormone proactin）被注入脑室后，会增加快速眼动睡眠（REM sleep），并引起大多数胆碱能神经元的持久兴奋。综上所述，除了对清醒时特别活跃的单胺能神经元的解除抑制外，下丘脑的神经激素因子（如催乳素）的输入也可能对产生快速眼动睡眠的胆碱能神经元产生兴奋。

It had long been suggested that cholinergic neurons in the laterodorsal tegmental nucleus of the brainstem play an important role in induction and maintenance of REM sleep. This was confirmed by studies in which single neuronal activity of the cholinergic neurons was recorded in undrugged animals repeating sleep and wakefulness ; among the studies our study using rats was characterized by in vivo identification of spike activity of the cholinergic neurons with their spike configuration to be broader than other neurons. The present study is then to clarify which neurons drive the cholinergic neurons. Rats were used in all experiments.First, whether, or how, the cholinergic neurons responded to electrical stimulation of the frontal cortex, preoptic area, mammillary body of the posterior hypothalamus, thalamus or hippocampus was examined. Most frequently they were driven orthodromically from the hypothalamic sites (preoptic area and mammillary body). Antidromic responses were obtained most frequently also from the preoptic area. These results suggest that the hypothalamus and brainstem cooperate with each other in controlling sleep and wakefulness.Then, responses of the cholinergic neurons to locally applied transmitters were examined. All subgroups of the cholinergic neurons, which were classified with their behavior during sleep and wakefulness, were inhibited by noradrenaline, being different from the neurons in the cats. Histamine had an excitatory action. Hypothalamic neurohormon prolactin, which had been known to increase REM sleep when injected into the cerebral ventricle, induced long-lasting excitation of most cholinergic neurons.In summary, excitation of the cholinergic neurons which produce REM sleep may be exerted, in addition to disinhibition from monoaminergic neurons active specifically during wakefulness, by inputs from the hypothalamus with neurohormonal factors such as prolactin.