藍班核 (Locus ceoruleus; 簡稱LC) 位於橋腦背側面,主要含有分泌正腎上腺素的神經元 (簡稱LC神經元)。LC神經元對大腦有非常廣泛的正腎上腺素纖維投射,因此在大腦功能狀態的調節上扮演極重要的角色,包括睡眠-清醒狀態與痛覺傳遞的調節。LC神經元具有節律性自發放電的行為並且其頻率與型式特徵具有日週期性的變化;LC神經元的放電頻率在清醒時期最為活躍,在非快速動眼睡眠期較為減弱,在快速動眼睡眠期則完全停止放射動作電位。過去在腦薄片研究顯示, GABAB受器所調節的持續性抑制作用(tonic inhibition)對於LC神經元自發性放電頻率有顯著性的影響。於是,我們提出一個GABA投射可能是直接成為這個睡眠依賴的LC神經元不活化的原因。為了測試這個假說,我們以麻醉大鼠為實驗動物,並且利用了一個新的方法結合了多種波動描記器,微電離子導入及單一單位記錄。我們發現以電離子導入CGP 35348,一種GABAB受器拮抗劑造成LC神經元自發性放電頻率的增加,以及從麻醉催眠至清醒的潛伏期縮短。根據以上的結果,我們可以得到一個結論:GABAB受器所調節的持續性抑制作用可能在調節睡眠-清醒週期性上扮演一個重要的角色。
The locus coeruleus (LC) locates in the rostral dorsolateral pontine tegmentum and consists of tightly packed noradrenergic neurons. LC neurons give rise to extensive axonal projections throughout many regions of the central nervous system and play an important role in regulation of multiple physiological processes, including sleep-waking state and pain control. Noradrenergic neurons in the LC appear to fire action potentials spontaneously and exhibit a circadian rhythm in impulse activity, which display active firing during wakefulness and a decreased discharge rate during non-rapid eye movement (non-REM) sleep and are silent during REM sleep. Previous studies indicated that LC neurons are subject to tonic inhibition mediated by GABAB receptors (GABABRs), and manipulating this GABABR-mediated tonic inhibition can effectively tune the frequency of LC neuron firing. It has been proposed that a GABAergic input could be directly responsible for this sleep-dependent neuronal inactivation. To test this hypothesis, we used a new method combining polygraphic recordings, microiontophoresis and single-unit recordings in anaesthetized rats. We found that iontophoretic application of CGP 35348, a specific GABAB-receptor antagonist induced an increase of the spontaneous firing rate, and a decrease of recovery latency from anesthetic hypnosis to arousal state. Based on these results, we conclude that GABABR-mediated inhibition could be an import player in the regulation of sleep-waking rhythm.