Strecker R E, Nalwalk J, Dauphin L J, Thakkar M M, Chen Y, Ramesh V, Hough L B, McCarley R W
Department of Psychiatry, VA Boston Healthcare System and Harvard Medical School, Research, 151C, 940 Belmont Street, Brockton, MA 02301, USA.
Neuroscience. 2002;113(3):663-70. doi: 10.1016/s0306-4522(02)00158-6.
Increased activity of the histaminergic neurons of the posterior hypothalamus has been implicated in the facilitation of behavioral wakefulness. Recent evidence of reciprocal projections between the sleep-active neurons of the preoptic/anterior hypothalamus and the histaminergic neurons of the tuberomammillary nucleus suggests that histaminergic innervation of the preoptic/anterior hypothalamic area may be of particular importance in the wakefulness-promoting properties of histamine. To test this possibility, we used microdialysis sample collection in the preoptic/anterior hypothalamic area of cats during natural sleep-wakefulness cycles, 6 h of sleep deprivation induced by gentle handling/playing, and recovery sleep. Samples were analyzed by a sensitive radioenzymatic assay. Mean basal levels of histamine in microdialysate during periods of wakefulness (1.155+/-0.225 pg/microl) did not vary during the 6 h of sleep deprivation. However, during the different sleep states, dramatic changes were observed in the extracellular histamine levels of preoptic/anterior hypothalamic area: wakefulness>non-rapid eye movement sleep>rapid eye movement sleep. Levels of histamine during rapid eye movement sleep were lowest (0.245+/-0.032 pg/microl), being significantly lower than levels during non-rapid eye movement sleep (0.395+/-0.081 pg/microl) and being only 21% of wakefulness levels. This pattern of preoptic/anterior hypothalamic area extracellular histamine levels across the sleep-wakefulness cycle closely resembles the reported single unit activity of histaminergic neurons. However, the invariance of histamine levels during sleep deprivation suggests that changes in histamine level do not relay information about sleep drive to the sleep-promoting neurons of the preoptic/anterior hypothalamic area.
下丘脑后部组胺能神经元活动增强与行为觉醒的促进有关。视前区/下丘脑前部睡眠活跃神经元与结节乳头体核组胺能神经元之间存在相互投射的最新证据表明，视前区/下丘脑前部区域的组胺能神经支配在组胺促进觉醒的特性中可能特别重要。为了验证这一可能性，我们在猫的视前区/下丘脑前部区域进行了微透析样本采集，监测自然睡眠-觉醒周期、轻柔处理/玩耍诱导的6小时睡眠剥夺以及恢复睡眠期间的情况。样本通过灵敏的放射酶测定法进行分析。觉醒期间微透析液中组胺的平均基础水平（1.155±0.225 pg/μl）在6小时睡眠剥夺期间没有变化。然而，在不同睡眠状态下，视前区/下丘脑前部区域的细胞外组胺水平出现了显著变化：觉醒>非快速眼动睡眠>快速眼动睡眠。快速眼动睡眠期间的组胺水平最低（0.245±0.032 pg/μl），显著低于非快速眼动睡眠期间的水平（0.395±0.081 pg/μl），仅为觉醒水平的21%。视前区/下丘脑前部区域细胞外组胺水平在睡眠-觉醒周期中的这种模式与报道的组胺能神经元的单单位活动非常相似。然而，睡眠剥夺期间组胺水平的不变性表明，组胺水平的变化不会将有关睡眠驱动力的信息传递给视前区/下丘脑前部区域促进睡眠的神经元。
