Opposite functions of histamine H1 and H2 receptors and H3 receptor in substantia nigra pars reticulata

Fuwen Zhou, Jian Jun Xu, Yu Zhao, Mark Ledoux, Fuming Zhou

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

The substantia nigra pars reticulata (SNr) is a key basal ganglia output nucleus. Inhibitory outputs from SNr are encoded in spike frequency and pattern of the inhibitory SNr projection neurons. SNr output intensity and pattern are often abnormal in movement disorders of basal ganglia origin. In Parkinson's disease, histamine innervation and histamine H3 receptor expression in SNr may be increased. However, the functional consequences of these alterations are not known. In this study, whole cell patch-clamp recordings were used to elucidate the function of different histamine receptors in SNr. Histamine increased SNr inhibitory projection neuron firing frequency and thus inhibitory output. This effect was mediated by activation of histamine H 1 and H2 receptors that induced inward currents and depolarization. In contrast, histamine H3 receptor activation hyperpolarized and inhibited SNr inhibitory projection neurons, thus decreasing the intensity of basal ganglia output. By the hyperpolarization, H3 receptor activation also increased the irregularity of the interspike intervals or changed the pattern of SNr inhibitory neuron firing. H3 receptor-mediated effects were normally dominated by those mediated by H 1 and H2 receptors. Furthermore, endogenously released histamine provided a tonic, H1 and H2 receptor-mediated excitation that helped keep SNr inhibitory projection neurons sufficiently depolarized and spiking regularly. These results suggest that H1 and H2 receptors and H3 receptor exert opposite effects on SNr inhibitory projection neurons. Functional balance of these different histamine receptors may contribute to the proper intensity and pattern of basal ganglia output and, as a consequence, exert important effects on motor control.

Original languageEnglish (US)
Pages (from-to)1581-1591
Number of pages11
JournalJournal of Neurophysiology
Volume96
Issue number3
DOIs
StatePublished - Sep 18 2006

Fingerprint

Histamine H3 Receptors
Histamine H1 Receptors
Histamine H2 Receptors
Basal Ganglia
Neurons
Histamine
Histamine Receptors
Pars Reticulata
Dyskinesias
Movement Disorders
Parkinson Disease

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Physiology

Cite this

Opposite functions of histamine H1 and H2 receptors and H3 receptor in substantia nigra pars reticulata. / Zhou, Fuwen; Xu, Jian Jun; Zhao, Yu; Ledoux, Mark; Zhou, Fuming.

In: Journal of Neurophysiology, Vol. 96, No. 3, 18.09.2006, p. 1581-1591.

Research output: Contribution to journalArticle

@article{82a7cfb613594e2ebf51c8f18fc73946,
title = "Opposite functions of histamine H1 and H2 receptors and H3 receptor in substantia nigra pars reticulata",
abstract = "The substantia nigra pars reticulata (SNr) is a key basal ganglia output nucleus. Inhibitory outputs from SNr are encoded in spike frequency and pattern of the inhibitory SNr projection neurons. SNr output intensity and pattern are often abnormal in movement disorders of basal ganglia origin. In Parkinson's disease, histamine innervation and histamine H3 receptor expression in SNr may be increased. However, the functional consequences of these alterations are not known. In this study, whole cell patch-clamp recordings were used to elucidate the function of different histamine receptors in SNr. Histamine increased SNr inhibitory projection neuron firing frequency and thus inhibitory output. This effect was mediated by activation of histamine H 1 and H2 receptors that induced inward currents and depolarization. In contrast, histamine H3 receptor activation hyperpolarized and inhibited SNr inhibitory projection neurons, thus decreasing the intensity of basal ganglia output. By the hyperpolarization, H3 receptor activation also increased the irregularity of the interspike intervals or changed the pattern of SNr inhibitory neuron firing. H3 receptor-mediated effects were normally dominated by those mediated by H 1 and H2 receptors. Furthermore, endogenously released histamine provided a tonic, H1 and H2 receptor-mediated excitation that helped keep SNr inhibitory projection neurons sufficiently depolarized and spiking regularly. These results suggest that H1 and H2 receptors and H3 receptor exert opposite effects on SNr inhibitory projection neurons. Functional balance of these different histamine receptors may contribute to the proper intensity and pattern of basal ganglia output and, as a consequence, exert important effects on motor control.",
author = "Fuwen Zhou and Xu, {Jian Jun} and Yu Zhao and Mark Ledoux and Fuming Zhou",
year = "2006",
month = "9",
day = "18",
doi = "10.1152/jn.00148.2006",
language = "English (US)",
volume = "96",
pages = "1581--1591",
journal = "Journal of Neurophysiology",
issn = "0022-3077",
publisher = "American Physiological Society",
number = "3",

}

TY - JOUR

T1 - Opposite functions of histamine H1 and H2 receptors and H3 receptor in substantia nigra pars reticulata

AU - Zhou, Fuwen

AU - Xu, Jian Jun

AU - Zhao, Yu

AU - Ledoux, Mark

AU - Zhou, Fuming

PY - 2006/9/18

Y1 - 2006/9/18

N2 - The substantia nigra pars reticulata (SNr) is a key basal ganglia output nucleus. Inhibitory outputs from SNr are encoded in spike frequency and pattern of the inhibitory SNr projection neurons. SNr output intensity and pattern are often abnormal in movement disorders of basal ganglia origin. In Parkinson's disease, histamine innervation and histamine H3 receptor expression in SNr may be increased. However, the functional consequences of these alterations are not known. In this study, whole cell patch-clamp recordings were used to elucidate the function of different histamine receptors in SNr. Histamine increased SNr inhibitory projection neuron firing frequency and thus inhibitory output. This effect was mediated by activation of histamine H 1 and H2 receptors that induced inward currents and depolarization. In contrast, histamine H3 receptor activation hyperpolarized and inhibited SNr inhibitory projection neurons, thus decreasing the intensity of basal ganglia output. By the hyperpolarization, H3 receptor activation also increased the irregularity of the interspike intervals or changed the pattern of SNr inhibitory neuron firing. H3 receptor-mediated effects were normally dominated by those mediated by H 1 and H2 receptors. Furthermore, endogenously released histamine provided a tonic, H1 and H2 receptor-mediated excitation that helped keep SNr inhibitory projection neurons sufficiently depolarized and spiking regularly. These results suggest that H1 and H2 receptors and H3 receptor exert opposite effects on SNr inhibitory projection neurons. Functional balance of these different histamine receptors may contribute to the proper intensity and pattern of basal ganglia output and, as a consequence, exert important effects on motor control.

AB - The substantia nigra pars reticulata (SNr) is a key basal ganglia output nucleus. Inhibitory outputs from SNr are encoded in spike frequency and pattern of the inhibitory SNr projection neurons. SNr output intensity and pattern are often abnormal in movement disorders of basal ganglia origin. In Parkinson's disease, histamine innervation and histamine H3 receptor expression in SNr may be increased. However, the functional consequences of these alterations are not known. In this study, whole cell patch-clamp recordings were used to elucidate the function of different histamine receptors in SNr. Histamine increased SNr inhibitory projection neuron firing frequency and thus inhibitory output. This effect was mediated by activation of histamine H 1 and H2 receptors that induced inward currents and depolarization. In contrast, histamine H3 receptor activation hyperpolarized and inhibited SNr inhibitory projection neurons, thus decreasing the intensity of basal ganglia output. By the hyperpolarization, H3 receptor activation also increased the irregularity of the interspike intervals or changed the pattern of SNr inhibitory neuron firing. H3 receptor-mediated effects were normally dominated by those mediated by H 1 and H2 receptors. Furthermore, endogenously released histamine provided a tonic, H1 and H2 receptor-mediated excitation that helped keep SNr inhibitory projection neurons sufficiently depolarized and spiking regularly. These results suggest that H1 and H2 receptors and H3 receptor exert opposite effects on SNr inhibitory projection neurons. Functional balance of these different histamine receptors may contribute to the proper intensity and pattern of basal ganglia output and, as a consequence, exert important effects on motor control.

UR - http://www.scopus.com/inward/record.url?scp=33748565950&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748565950&partnerID=8YFLogxK

U2 - 10.1152/jn.00148.2006

DO - 10.1152/jn.00148.2006

M3 - Article

VL - 96

SP - 1581

EP - 1591

JO - Journal of Neurophysiology

JF - Journal of Neurophysiology

SN - 0022-3077

IS - 3

ER -