Identification of a histaminergic circuit in the caudal hypothalamus: An evidence for functional heterogeneity of histaminergic neurons |
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Authors: | Hayato Umehara Hiroyuki MizuguchiHiroyuki Fukui |
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Affiliation: | Department of Molecular Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan |
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Abstract: | It is well established that histaminergic neurons in the posterior hypothalamus make connections with whole brain areas and regulate several functions. Recent evidence indicates that histaminergic neurons are heterogeneous cell group and organized into distinct circuits. However, functional circuits of histaminergic neurons have not been fully mapped so far. To address this issue, we have investigated antihistamine-sensitive neuronal activation in the hypothalamus to determine the hypothalamic region primarily innervated by histaminergic neurons. Here we review our recent findings showing the existence of the heterogeneous subpopulations of histaminergic neurons in the TMN that innervated distinct regions to regulate particular functions. We have identified the caudal part of the arcuate nucleus of hypothalamus (cARC) as a target region of histaminergic neurons in food-restricted rats by assessing suppression of c-Fos expression by pretreatment with antihistamines. Histaminergic neurons in the tuberomammillary nucleus (TMN) are morphologically subdivided into five groups (E1–E5). Among the subdivisions, the E3 group was found to be activated corresponding to the activation of cARC neurons. Our findings suggest that this subpopulation selectively innervate cARC neurons. Accumulating reports have also described c-Fos expression in other TMN subpopulations. Various stress challenge induced c-Fos expression primarily in E4 and E5 subpopulations. Motivation- and drug-induced arousal elicited in common activation of ventrolateral part of the TMN containing E1 and E2 subdivisions, which receive projections from wake-active orexin neurons and sleep-active GABA neurons. These lines of evidence support the hypothesis that there are heterogeneous subpopulations in the TMN that innervated distinct regions to regulate particular functions. |
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Keywords: | ARC, arcuate nucleus of hypothalamus H1R, histamine H1 receptor H2R, histamine H2 receptor H3R, histamine H3 receptor HDC, histidine decarboxylase IR, immunoreactivity LH, lateral hypothalamus MPO, medial preoptic area MSH, α-melanocyte stimulating hormone NPY, neuropeptide Y POA, Preoptic area POMC, proopiomelanocortin PVH, paraventricular nucleus of hypothalamus TMN, tuberomammillary nuclei VMH, ventromedial nucleus of hypothalamus |
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