Structure and Functions of the Central Histaminergic Neuron System

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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.