Abstract
Histamine axons originate from a single source, the tuberomamillary nucleus (TMN) of the posterior hypothalamus, to innervate almost all central nervous system (CNS) regions. This feature, a compact cell group with widely distributed fibers, resembles that of other amine systems, such as noradrenaline or serotonin, and is consistent with a function for histamine over a host of physiological processes, including the regulation of the sleep-wake cycle, appetite, endocrine homeostasis, body temperature, pain perception, learning, memory, and emotion. An important question is whether these diverse physiological roles are served by different histamine neuronal subpopulation. While the histamine system is generally regarded as one single functional unit that provides histamine throughout the brain, evidence is beginning to accumulate in favor of heterogeneity of histamine neurons. The aim of this review is to summarize experimental evidence demonstrating that histamine neurons are heterogeneous, organized into functionally distinct circuits, impinging on different brain regions, and displaying selective control mechanisms. This could imply independent functions of subsets of histamine neurons according to their respective origin and terminal projections.
Highlights
Histamine axons originate from a single source, the tuberomamillary nucleus (TMN) of the posterior hypothalamus, to innervate almost all central nervous system (CNS) regions
Stress-sensitive histamine neurons were detected in the rostral (E4–E5) subgroups rather than in the caudal ones (E1–E3), clearly indicating that histaminergic neurons of distinct TMN clusters are recruited in a stressor- and subgroup-specific manner (Miklos and Kovacs, 2003)
HISTAMINE NEURONS ESTABLISH FUNCTIONALLY DISTINCT PATHWAYS ACCORDING TO THEIR TERMINAL PROJECTIONS In our laboratory we addressed the question of whether histaminergic neurons are organized into distinct functional circuits impinging on different brain regions
Summary
Histamine neurons in the tuberomamillary nucleus: a whole center or distinct subpopulations?. The aim of this review is to summarize experimental evidence demonstrating that histamine neurons are heterogeneous, organized into functionally distinct circuits, impinging on different brain regions, and displaying selective control mechanisms This could imply independent functions of subsets of histamine neurons according to their respective origin and terminal projections. Histaminergic efferents present diffuse varicosities containing synaptic vesicles, but form synaptic contacts only infrequently (Takagi et al, 1986; Tohyama et al, 1991; Michelsen and Panula, 2002) This feature and the lack of a high-affinity uptake mechanism specific for histamine in the CNS suggest that histamine may diffuse from the site of release and has widespread effects, acting as a local hormone affecting neuronal, and glial activity and blood vessel tone (Wada et al, 1991b). Consistent with this hypothesis, heterogeneity within the histaminergic neuronal population in response to stress (Miklos and Kovacs, 2003) and pharmacological stimulations was recently reported (Blandina et al, 2010; Passani and Blandina, 2011)
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