Effects of glutamate agonist versus procaine microinjections into the basal forebrain cholinergic cell area upon gamma and theta EEG activity and sleep-wake state

Effects of glutamate agonist versus procaine microinjections into the basal forebrain cholinergic cell area upon gamma and theta EEG activity and sleep-wake state
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DOI:
10.1046/j.1460-9568.2000.00099.x
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发表时间:
2000-06-01
影响因子:
3.4
通讯作者:
Jones, BE
Jones, BE
中科院分区:
医学3区
文献类型:
--
作者:
Cape, EG;Jones, BE

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作为从脑干网状激活系统到大脑皮层的腹侧丘脑外中继,基底前脑神经元,重要的是其中的胆碱能细胞,被认为在清醒和反常睡眠状态期间引发和维持皮质激活方面发挥着重要作用。本研究在大鼠中进行,旨在检查微量注射普鲁卡因灭活基底前脑神经元与微量注射谷氨酸激动剂(脑干网状激活系统的主要神经递质)激活基底前脑神经元对脑电图(EEG)活动和睡眠-觉醒状态的影响。白天大部分时间都在睡觉时,使用远程控制装置对自由活动、自然睡眠/醒来的大鼠进行基底前脑显微注射。普鲁卡因导致伽马(30-60赫兹)和西塔(4-8赫兹)脑电图活动减少,以及与反常睡眠丧失相关的δ(1-4赫兹)增加,尽管慢波睡眠持续存在。 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸 (AMPA) 和 N-甲基-D-天冬氨酸 (NMDA) 会增加 γ 值并减少 δ 值,同时引起清醒。此外,NMDA 在体外已被证明可诱导胆碱能细胞的节律性爆发,显着增加 θ 活性。显微注射 NMDA 后,在显微注射插管附近的无名质和大细胞视前核中的大量胆碱能神经元以及 GABA 能神经元(γ-氨基丁酸)和其他非胆碱能神经元中发现了 c-Fos 蛋白,该蛋白已被证明可以反映神经活动。这些结果证实了胆碱能神经元(可能与其他基底前脑神经元一起)在皮质激活中的作用,包括在清醒和矛盾睡眠期间引发皮质唤醒的 γ 和 θ 活动。
Serving as the ventral, extra-thalamic relay from the brainstem reticular activating system to the cerebral cortex, basal forebrain neurons, including importantly the cholinergic cells therein, are believed to play a significant role in eliciting and maintaining cortical activation during the states of waking and paradoxical sleep. The present study was undertaken in rats to examine the effects upon electroencephalogram (EEG) activity and sleep-wake state of inactivating basal forebrain neurons with microinjections of procaine versus activating them with microinjections of agonists of glutamate, which is the primary neurotransmitter of the brainstem reticular activating system. Microinjections into the basal forebrain were performed using a remotely controlled device in freely moving, naturally sleeping/waking rats during the day when they are asleep the majority of the time. Procaine produced a decrease in gamma (30-60 Hz) and theta (4-8 Hz) EEG activities, and an increase in delta (1-4 Hz) associated with a loss of paradoxical sleep, despite the persistence of slow wave sleep. alpha-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) produced an increase in gamma and a decrease in delta, while eliciting waking, In addition, NMDA, which has been shown in vitro to induce rhythmic bursting in the cholinergic cells, significantly increased theta activity. Following the microinjections of NMDA, c-Fos protein, which has been shown to reflect neural activity, was found in numerous cholinergic, and also GABAergic (gamma-aminobutyric acid) and other non-cholinergic neurons, in the substantia innominata and magnocellular preoptic nucleus near the microinjection cannulae. These results substantiate the role of cholinergic, possibly together with other, basal forebrain neurons in cortical activation, including elicitation of gamma and theta activities that underlie cortical arousal during waking and paradoxical sleep.