Structure and Functions of the Central Histaminergic Neuron System

中枢组胺能系统的胞体局限于下丘脑后部的结节乳头核，它们向整个脑区投射纤维。这种形态特征表明，组胺能系统与一些一般的和基本的神经功能有关。在这方面，我们通过以下4种策略探讨了组胺能系统的生理意义。(1)形态方法：中枢组胺能神经系统的详细图谱，该系统的系统发展，通过正电子发射断层扫描显示h1受体的体内可视化，原位杂交，(2)神经药理学和神经生理学方法：组胺在体外利用下丘脑切片制备和在体内使用微透析技术的释放机制，组胺在调节昼夜节律中的生理和病理生理意义，神经内分泌系统，摄食行为，体温，衰老，自发活动，抑郁，癫痫和运动病，(3)神经化学和细胞生物学方法：组胺合成和释放的调节机制，组胺受体的药理学特征，原代培养星形胶质细胞的受体表达和细胞内信号转导；(4)分子生物学方法：组胺H1受体、组氨酸脱羧酶、组胺N-甲基转移酶和多巴脱羧酶的克隆和表达。综上所述，结节乳头核中的组胺能神经元构成一个单一的功能单位，从其纤维末梢释放的组胺调节大脑广泛分化区域的活动，不仅作用于神经元，还作用于星形胶质细胞和血管。组胺能神经元系统是全脑活动的调节中心。

The cell bodies of the central histaminergic system were confined to the tuberomammillary nucleus in the posterior hypothalamic region and they project fibers to whole brain areas. This morphological characteristics suggest that the histaminergic system relate some general and fundamental neural functions. In this respect, we approached the physiological significance of the histaminergic system by following 4 strategies. (1) Morphological approach : detailed mapping of the central histaminergic neuronal system, phylogeny of the system, in vivo visualization of the H1-receptor by positron emission tomography, in situ hybridization, (2) Neuropharmacological and neurophysiological approach : release mechanism of histamine in vitro using hypothalamic slice preparation and in vivo using a microdialysis technique, physiological and pathophysiological significance of histamine in the regulation of circadian rhythm, neuroendocrine system, feeding behavior, body temperature, aging, spontaneous activity, depression, epilepsy and motion sickness, (3) Neurochemical and cell biological approach : regulation mechanism of histamine synthesis and release, pharmacological characterization of histamine receptors, receptor expression and intracellular signal transduction in primary cultured astrocytes, (4) Molecular biological approach : cloning and expression of histamine H1 receptor, histidine decarboxylase, histamine-N-methyltransferase and dopa decarboxylase.In conclusion, the histaminergic neurons in the tuberomammillary nucleus constitute a single functional unit and histamine released from their fiber terminals regulates the activities of widely divergent regions of the brain, acting not only on neurons but also on astrocytes and blood vessels. The histaminergic neuron system is a regulatory center for whole-brain activity.