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Postsynaptic mechanisms underlying the excitatory action of histamine on medial vestibular nucleus neurons in rats.

ABSTRACT: BACKGROUND AND PURPOSE: Anti-histaminergic drugs have been widely used in the clinical treatment of vestibular disorders and most studies concentrate on their presynaptic actions. The present study investigated the postsynaptic effect of histamine on medial vestibular nucleus (MVN) neurons and the underlying mechanisms. EXPERIMENTAL APPROACH: Histamine-induced postsynaptic actions on MVN neurons and the corresponding receptor and ionic mechanisms were detected by whole-cell patch-clamp recordings on rat brain slices. The distribution of postsynaptic histamine H?, H? and H? receptors was mapped by double and single immunostaining. Furthermore, the expression of mRNAs for H?, H? and H? receptors and for subtypes of Na? -Ca²? exchangers (NCXs) and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels was assessed by quantitative real-time RT-PCR. KEY RESULTS: A marked postsynaptic excitatory effect, co-mediated by histamine H? and H? receptors, was involved in the histamine-induced depolarization of MVN neurons. Postsynaptic H? and H? rather than H? receptors were co-localized in the same MVN neurons. NCXs contributed to the inward current mediated by H? receptors, whereas HCN channels were responsible for excitation induced by activation of H? receptors. Moreover, NCX1 and NCX3 rather than NCX2, and HCN1 rather than HCN2-4 mRNAs, were abundantly expressed in MVN. CONCLUSION AND IMPLICATIONS: NCXs coupled to H? receptors and HCN channels linked to H? receptors co-mediate the strong postsynaptic excitatory action of histamine on MVN neurons. These results highlight an active role of postsynaptic mechanisms in the modulation by central histaminergic systems of vestibular functions and suggest potential targets for clinical treatment of vestibular disorders.

SUBMITTER: Zhang XY

PROVIDER: S-EPMC3764857 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Postsynaptic mechanisms underlying the excitatory action of histamine on medial vestibular nucleus neurons in rats.

Zhang Xiao-Yang XY Yu Lei L Zhuang Qian-Xing QX Peng Shi-Yu SY Zhu Jing-Ning JN Wang Jian-Jun JJ

British journal of pharmacology 20130901 1

<h4>Background and purpose</h4>Anti-histaminergic drugs have been widely used in the clinical treatment of vestibular disorders and most studies concentrate on their presynaptic actions. The present study investigated the postsynaptic effect of histamine on medial vestibular nucleus (MVN) neurons and the underlying mechanisms.<h4>Experimental approach</h4>Histamine-induced postsynaptic actions on MVN neurons and the corresponding receptor and ionic mechanisms were detected by whole-cell patch-cl ...[more]

PMID: 23713466

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Project description:The dysfunction of the medial prefrontal cortex is associated with affective disorders and non-motor features in Parkinson's disease. However, the exact role of the mediodorsal thalamic nucleus in the function of the prefrontal cortex remains unclear. To study the possible effects of the mediodorsal thalamic nucleus on the neurological function of the medial prefrontal cortex, a model of Parkinson's disease was established by injecting 8 µg 6-hydroxydopamine into the substantia nigra compacta of rats. After 1 or 3 weeks, 0.3 µg ibotenic acid was injected into the mediodorsal thalamic nucleus of the midbrain. At 3 or 5 weeks after the initial injury, neuronal discharge in medial prefrontal cortex of rat brain was determined electrophysiologically. The numbers of dopamine-positive neurons and tyrosine hydroxylase immunoreactivity in substantia nigra compacta and ventral tegmental area were detected by immunohistochemical staining. Results demonstrated that after injury, the immunoreactivity of dopamine neurons and tyrosine hydroxylase decreased in the substantia nigra compacta and ventral tegmental areas of rats. Compared with normal medial prefrontal cortical neurons, at 3 and 5 weeks after substantia nigra compacta injury, the discharge frequency of pyramidal neurons increased and the discharge pattern of these neurons tended to be a burst-discharge, with an increased discharge interval. The discharge frequency of interneurons decreased and the discharge pattern also tended to be a burst-discharge, but the discharge interval was only higher at 3 weeks. At 3 weeks after the combined lesions, the discharge frequency, discharge pattern and discharge interval were restored to a normal level in pyramidal neurons and interneurons in medial prefrontal cortex. These findings have confirmed that mediodorsal thalamic nucleus is involved in regulating neuronal activities of the medial prefrontal cortex. The changes in the function of the mediodorsal thalamic nucleus may be associated with the abnormal discharge activity of the medial prefrontal cortex neurons after substantia nigra compacta injury. All experimental procedures were approved by the Institutional Animal Care and Use Committee of Xi'an Jiaotong University, China (approval No. XJTULAC2017-067) on August 26, 2017.

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Postsynaptic mechanisms underlying the excitatory action of histamine on medial vestibular nucleus neurons in rats.

Publications

Postsynaptic mechanisms underlying the excitatory action of histamine on medial vestibular nucleus neurons in rats.

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