Amygdalar Endothelin-1 Regulates Pyramidal Neuron Excitability and Affects Anxiety

Abstract An abnormal neuronal activity in the amygdala is involved in the pathogenesis of anxiety disorders. However, little is known about the mechanisms. High-anxiety mice and low-anxiety mice, representing the innate extremes of anxiety-related behaviors, were first grouped according to their anx...

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Autores principales:	Ming Chen, Huan-huan Yan, Shu Shu, Lei Pei, Long-kai Zang, Yu Fu, Ze-fen Wang, Qi Wan, Lin-lin Bi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/89036116fe3b438d90d5e0d762c2ff6c
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spelling	oai:doaj.org-article:89036116fe3b438d90d5e0d762c2ff6c2021-12-02T11:41:19ZAmygdalar Endothelin-1 Regulates Pyramidal Neuron Excitability and Affects Anxiety10.1038/s41598-017-02583-62045-2322https://doaj.org/article/89036116fe3b438d90d5e0d762c2ff6c2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02583-6https://doaj.org/toc/2045-2322Abstract An abnormal neuronal activity in the amygdala is involved in the pathogenesis of anxiety disorders. However, little is known about the mechanisms. High-anxiety mice and low-anxiety mice, representing the innate extremes of anxiety-related behaviors, were first grouped according to their anxiety levels in the elevated plus maze test. We found that the mRNA for endothelin-1 (ET1) and ET1 B-type receptors (ETBRs) in the amygdala was down-regulated in high-anxiety mice compared with low-anxiety mice. Knocking down basolateral amygdala (BLA) ET1 expression enhanced anxiety-like behaviors, whereas over-expressing ETBRs, but not A-type receptors (ETARs), had an anxiolytic effect. The combined down-regulation of ETBR and ET1 had no additional anxiogenic effect compared to knocking down the ETBR gene alone, suggesting that BLA ET1 acts through ETBRs to regulate anxiety-like behaviors. To explore the mechanism underlying this phenomenon further, we verified that most of the ET1 and the ET1 receptors in the BLA were expressed in pyramidal neurons. The ET1–ETBR signaling pathway decreased the firing frequencies and threshold currents for the action potentials of BLA pyramidal neurons but did not alter BLA synaptic neurotransmission. Together, these results indicate that amygdalar ET1-ETBR signaling could attenuate anxiety-like behaviors by directly decreasing the excitability of glutamatergic neurons.Ming ChenHuan-huan YanShu ShuLei PeiLong-kai ZangYu FuZe-fen WangQi WanLin-lin BiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ming Chen Huan-huan Yan Shu Shu Lei Pei Long-kai Zang Yu Fu Ze-fen Wang Qi Wan Lin-lin Bi Amygdalar Endothelin-1 Regulates Pyramidal Neuron Excitability and Affects Anxiety
description	Abstract An abnormal neuronal activity in the amygdala is involved in the pathogenesis of anxiety disorders. However, little is known about the mechanisms. High-anxiety mice and low-anxiety mice, representing the innate extremes of anxiety-related behaviors, were first grouped according to their anxiety levels in the elevated plus maze test. We found that the mRNA for endothelin-1 (ET1) and ET1 B-type receptors (ETBRs) in the amygdala was down-regulated in high-anxiety mice compared with low-anxiety mice. Knocking down basolateral amygdala (BLA) ET1 expression enhanced anxiety-like behaviors, whereas over-expressing ETBRs, but not A-type receptors (ETARs), had an anxiolytic effect. The combined down-regulation of ETBR and ET1 had no additional anxiogenic effect compared to knocking down the ETBR gene alone, suggesting that BLA ET1 acts through ETBRs to regulate anxiety-like behaviors. To explore the mechanism underlying this phenomenon further, we verified that most of the ET1 and the ET1 receptors in the BLA were expressed in pyramidal neurons. The ET1–ETBR signaling pathway decreased the firing frequencies and threshold currents for the action potentials of BLA pyramidal neurons but did not alter BLA synaptic neurotransmission. Together, these results indicate that amygdalar ET1-ETBR signaling could attenuate anxiety-like behaviors by directly decreasing the excitability of glutamatergic neurons.
format	article
author	Ming Chen Huan-huan Yan Shu Shu Lei Pei Long-kai Zang Yu Fu Ze-fen Wang Qi Wan Lin-lin Bi
author_facet	Ming Chen Huan-huan Yan Shu Shu Lei Pei Long-kai Zang Yu Fu Ze-fen Wang Qi Wan Lin-lin Bi
author_sort	Ming Chen
title	Amygdalar Endothelin-1 Regulates Pyramidal Neuron Excitability and Affects Anxiety
title_short	Amygdalar Endothelin-1 Regulates Pyramidal Neuron Excitability and Affects Anxiety
title_full	Amygdalar Endothelin-1 Regulates Pyramidal Neuron Excitability and Affects Anxiety
title_fullStr	Amygdalar Endothelin-1 Regulates Pyramidal Neuron Excitability and Affects Anxiety
title_full_unstemmed	Amygdalar Endothelin-1 Regulates Pyramidal Neuron Excitability and Affects Anxiety
title_sort	amygdalar endothelin-1 regulates pyramidal neuron excitability and affects anxiety
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/89036116fe3b438d90d5e0d762c2ff6c
work_keys_str_mv	AT mingchen amygdalarendothelin1regulatespyramidalneuronexcitabilityandaffectsanxiety AT huanhuanyan amygdalarendothelin1regulatespyramidalneuronexcitabilityandaffectsanxiety AT shushu amygdalarendothelin1regulatespyramidalneuronexcitabilityandaffectsanxiety AT leipei amygdalarendothelin1regulatespyramidalneuronexcitabilityandaffectsanxiety AT longkaizang amygdalarendothelin1regulatespyramidalneuronexcitabilityandaffectsanxiety AT yufu amygdalarendothelin1regulatespyramidalneuronexcitabilityandaffectsanxiety AT zefenwang amygdalarendothelin1regulatespyramidalneuronexcitabilityandaffectsanxiety AT qiwan amygdalarendothelin1regulatespyramidalneuronexcitabilityandaffectsanxiety AT linlinbi amygdalarendothelin1regulatespyramidalneuronexcitabilityandaffectsanxiety
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Amygdalar Endothelin-1 Regulates Pyramidal Neuron Excitability and Affects Anxiety

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