Berridge C W, Page M E, Valentino R J, Foote S L
Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla 92093.
Neuroscience. 1993 Jul;55(2):381-93. doi: 10.1016/0306-4522(93)90507-c.
The effects of inhibition of locus coeruleus neuronal discharge activity on cortical and hippocampal electroencephalographic activity were examined in halothane-anesthetized rats. A combined recording/infusion probe was used to place 35-150-nl infusions of the alpha 2-noradrenergic agonist, clonidine (1 ng/nl) which inhibits locus coeruleus neuronal discharge activity, immediately adjacent to the locus coeruleus. The recording electrode allowed verification and quantification of the electrophysiological effects of these infusions. Simultaneously, electroencephalographic activity was recorded from sites in frontal neocortex and dorsal hippocampus and subjected to power spectrum analyses. Neither cortical nor hippocampal electroencephalographic activity was substantially affected following unilateral locus coeruleus inactivation. In contrast, bilateral clonidine infusions that completely suppressed locus coeruleus neuronal discharge activity in both hemispheres altered cortical and hippocampal electroencephalographic status. The cortical response to bilateral LC inhibition was characterized by a shift from low-amplitude, high-frequency to large-amplitude, slow-wave activity. Additionally, theta-dominated activity in the hippocampus was replaced with mixed frequency activity. The onset of these changes in forebrain electroencephalographic activity was coincident with the complete bilateral inhibition of locus coeruleus neuronal discharge activity. The resumption of pre-infusion electroencephalographic patterns closely followed recovery of locus coeruleus neuronal activity or could be induced with systemic administration of the alpha 2-noradrenergic antagonist, idazoxan. Clonidine infusions placed 800-1200 microns from the locus coeruleus were less effective at inducing a complete suppression of locus coeruleus activity. These infusions either did not completely inhibit locus coeruleus discharge (35 nl infusions), or did so with a longer latency to complete locus coeruleus inhibition and a shorter duration of inhibition (150 nl infusions). Changes in forebrain electroencephalographic activity occurred only following the complete bilateral suppression of locus coeruleus neuronal discharge activity. These electroencephalographic responses closely followed or coincided with the onset of complete bilateral locus coeruleus inhibition and persisted throughout the period during which bilateral LC neuronal discharge activity was completely absent (60-240 min). Recovery of electroencephalographic patterns was coincident with the reappearance of locus coeruleus discharge activity. These results suggest that the clonidine-induced changes in forebrain electroencephalographic activity were dependent on the complete bilateral suppression of locus coeruleus discharge activity, and that under the present experimental conditions the locus coeruleus/noradrenergic system exerts a potent and tonic activating influence on forebrain electroencephalographic state. These results support the hypothesis that this system may be an important modulator of behavioral state and/or state-dependent processes.
在氟烷麻醉的大鼠中，研究了蓝斑神经元放电活动受抑制对皮质和海马脑电图活动的影响。使用联合记录/灌注探针，将35 - 150 nl的α2 - 去甲肾上腺素能激动剂可乐定（1 ng/nl）灌注到紧邻蓝斑的位置，可乐定可抑制蓝斑神经元放电活动。记录电极用于验证和量化这些灌注的电生理效应。同时，从额叶新皮质和背侧海马的部位记录脑电图活动，并进行功率谱分析。单侧蓝斑失活后，皮质和海马的脑电图活动均未受到实质性影响。相反，双侧灌注可乐定完全抑制了双侧蓝斑神经元放电活动，改变了皮质和海马的脑电图状态。皮质对双侧蓝斑抑制的反应表现为从低振幅、高频活动转变为高振幅、慢波活动。此外，海马中以θ波为主的活动被混合频率活动所取代。前脑脑电图活动的这些变化与蓝斑神经元放电活动的完全双侧抑制同时发生。灌注前脑电图模式的恢复紧跟蓝斑神经元活动的恢复，或者可以通过全身给予α2 - 去甲肾上腺素能拮抗剂咪唑克生诱导恢复。在距蓝斑800 - 1200微米处灌注可乐定，诱导蓝斑活动完全抑制的效果较差。这些灌注要么不能完全抑制蓝斑放电（35 nl灌注），要么完全抑制蓝斑放电的潜伏期较长且抑制持续时间较短（150 nl灌注）。前脑脑电图活动的变化仅在蓝斑神经元放电活动完全双侧抑制后出现。这些脑电图反应紧跟或与双侧蓝斑完全抑制的开始同时发生，并在双侧蓝斑神经元放电活动完全消失的期间（60 - 240分钟）持续存在。脑电图模式的恢复与蓝斑放电活动的重新出现同时发生。这些结果表明，可乐定诱导的前脑脑电图活动变化依赖于蓝斑放电活动的完全双侧抑制，并且在当前实验条件下，蓝斑/去甲肾上腺素能系统对前脑脑电图状态施加了强大的、持续性的激活影响。这些结果支持了这样一种假设，即该系统可能是行为状态和/或状态依赖性过程的重要调节因子。
