Amygdala NRG1-ErbB4 is critical for the modulation of anxiety-like behaviors

Lin Lin Bi, Xiang Dong Sun, Jie Zhang, Yisheng Lu, Yi Hua Chen, Jue Wang, Fei Geng, Fang Liu, Meng Zhang, Ji Hong Liu, Xiao Wen Li, Lin Mei, Tian Ming Gao

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Anxiety disorder is related to the pathophysiology of psychiatric diseases, including major depression, substance abuse, and schizophrenia. The amygdala is important for manifestation and modulation of anxiety. However, relatively little is known regarding the mechanisms that control the amygdala inhibitory activity that is involved in anxiety. We found that almost all ErbB4, which is the only autonomous receptor of neuregulin 1 (NRG1) in the basolateral amygdala (BLA), was expressed in GABAergic neurons. Endogenous NRG1-ErbB4 signaling pathway in the BLA could modulate anxiety-like behaviors and GABA release, whereas it had no effect on glutamatergic transmission. The administration of NRG1 into the BLA of high-anxiety mice alleviated their anxiety and enhanced GABAergic neurotransmission. Moreover, exogenous NRG1 also produced an anxiolytic effect in the stressed mice. Together, these observations indicated that NRG1-ErbB4 signaling is critical to maintaining GABAergic activity in the amygdala and thus to modulating anxiety-like behaviors. Because NRG1 and ErbB4 are susceptibility genes of schizophrenia, our findings might also help to explain the potential mechanism of emotional abnormality in schizophrenia.

Original languageEnglish (US)
Pages (from-to)974-986
Number of pages13
JournalNeuropsychopharmacology
Volume40
Issue number4
DOIs
StatePublished - Jan 1 2015

Fingerprint

Neuregulin-1
Amygdala
Anxiety
Schizophrenia
GABAergic Neurons
Anti-Anxiety Agents
Anxiety Disorders
Synaptic Transmission
gamma-Aminobutyric Acid
Substance-Related Disorders
Psychiatry
Depression
Genes
Basolateral Nuclear Complex

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Bi, L. L., Sun, X. D., Zhang, J., Lu, Y., Chen, Y. H., Wang, J., ... Gao, T. M. (2015). Amygdala NRG1-ErbB4 is critical for the modulation of anxiety-like behaviors. Neuropsychopharmacology, 40(4), 974-986. https://doi.org/10.1038/npp.2014.274

Amygdala NRG1-ErbB4 is critical for the modulation of anxiety-like behaviors. / Bi, Lin Lin; Sun, Xiang Dong; Zhang, Jie; Lu, Yisheng; Chen, Yi Hua; Wang, Jue; Geng, Fei; Liu, Fang; Zhang, Meng; Liu, Ji Hong; Li, Xiao Wen; Mei, Lin; Gao, Tian Ming.

In: Neuropsychopharmacology, Vol. 40, No. 4, 01.01.2015, p. 974-986.

Research output: Contribution to journalArticle

Bi, LL, Sun, XD, Zhang, J, Lu, Y, Chen, YH, Wang, J, Geng, F, Liu, F, Zhang, M, Liu, JH, Li, XW, Mei, L & Gao, TM 2015, 'Amygdala NRG1-ErbB4 is critical for the modulation of anxiety-like behaviors', Neuropsychopharmacology, vol. 40, no. 4, pp. 974-986. https://doi.org/10.1038/npp.2014.274
Bi, Lin Lin ; Sun, Xiang Dong ; Zhang, Jie ; Lu, Yisheng ; Chen, Yi Hua ; Wang, Jue ; Geng, Fei ; Liu, Fang ; Zhang, Meng ; Liu, Ji Hong ; Li, Xiao Wen ; Mei, Lin ; Gao, Tian Ming. / Amygdala NRG1-ErbB4 is critical for the modulation of anxiety-like behaviors. In: Neuropsychopharmacology. 2015 ; Vol. 40, No. 4. pp. 974-986.
@article{756e303f3e904bbc80ce0332444bed94,
title = "Amygdala NRG1-ErbB4 is critical for the modulation of anxiety-like behaviors",
abstract = "Anxiety disorder is related to the pathophysiology of psychiatric diseases, including major depression, substance abuse, and schizophrenia. The amygdala is important for manifestation and modulation of anxiety. However, relatively little is known regarding the mechanisms that control the amygdala inhibitory activity that is involved in anxiety. We found that almost all ErbB4, which is the only autonomous receptor of neuregulin 1 (NRG1) in the basolateral amygdala (BLA), was expressed in GABAergic neurons. Endogenous NRG1-ErbB4 signaling pathway in the BLA could modulate anxiety-like behaviors and GABA release, whereas it had no effect on glutamatergic transmission. The administration of NRG1 into the BLA of high-anxiety mice alleviated their anxiety and enhanced GABAergic neurotransmission. Moreover, exogenous NRG1 also produced an anxiolytic effect in the stressed mice. Together, these observations indicated that NRG1-ErbB4 signaling is critical to maintaining GABAergic activity in the amygdala and thus to modulating anxiety-like behaviors. Because NRG1 and ErbB4 are susceptibility genes of schizophrenia, our findings might also help to explain the potential mechanism of emotional abnormality in schizophrenia.",
author = "Bi, {Lin Lin} and Sun, {Xiang Dong} and Jie Zhang and Yisheng Lu and Chen, {Yi Hua} and Jue Wang and Fei Geng and Fang Liu and Meng Zhang and Liu, {Ji Hong} and Li, {Xiao Wen} and Lin Mei and Gao, {Tian Ming}",
year = "2015",
month = "1",
day = "1",
doi = "10.1038/npp.2014.274",
language = "English (US)",
volume = "40",
pages = "974--986",
journal = "Neuropsychopharmacology",
issn = "0893-133X",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Amygdala NRG1-ErbB4 is critical for the modulation of anxiety-like behaviors

AU - Bi, Lin Lin

AU - Sun, Xiang Dong

AU - Zhang, Jie

AU - Lu, Yisheng

AU - Chen, Yi Hua

AU - Wang, Jue

AU - Geng, Fei

AU - Liu, Fang

AU - Zhang, Meng

AU - Liu, Ji Hong

AU - Li, Xiao Wen

AU - Mei, Lin

AU - Gao, Tian Ming

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Anxiety disorder is related to the pathophysiology of psychiatric diseases, including major depression, substance abuse, and schizophrenia. The amygdala is important for manifestation and modulation of anxiety. However, relatively little is known regarding the mechanisms that control the amygdala inhibitory activity that is involved in anxiety. We found that almost all ErbB4, which is the only autonomous receptor of neuregulin 1 (NRG1) in the basolateral amygdala (BLA), was expressed in GABAergic neurons. Endogenous NRG1-ErbB4 signaling pathway in the BLA could modulate anxiety-like behaviors and GABA release, whereas it had no effect on glutamatergic transmission. The administration of NRG1 into the BLA of high-anxiety mice alleviated their anxiety and enhanced GABAergic neurotransmission. Moreover, exogenous NRG1 also produced an anxiolytic effect in the stressed mice. Together, these observations indicated that NRG1-ErbB4 signaling is critical to maintaining GABAergic activity in the amygdala and thus to modulating anxiety-like behaviors. Because NRG1 and ErbB4 are susceptibility genes of schizophrenia, our findings might also help to explain the potential mechanism of emotional abnormality in schizophrenia.

AB - Anxiety disorder is related to the pathophysiology of psychiatric diseases, including major depression, substance abuse, and schizophrenia. The amygdala is important for manifestation and modulation of anxiety. However, relatively little is known regarding the mechanisms that control the amygdala inhibitory activity that is involved in anxiety. We found that almost all ErbB4, which is the only autonomous receptor of neuregulin 1 (NRG1) in the basolateral amygdala (BLA), was expressed in GABAergic neurons. Endogenous NRG1-ErbB4 signaling pathway in the BLA could modulate anxiety-like behaviors and GABA release, whereas it had no effect on glutamatergic transmission. The administration of NRG1 into the BLA of high-anxiety mice alleviated their anxiety and enhanced GABAergic neurotransmission. Moreover, exogenous NRG1 also produced an anxiolytic effect in the stressed mice. Together, these observations indicated that NRG1-ErbB4 signaling is critical to maintaining GABAergic activity in the amygdala and thus to modulating anxiety-like behaviors. Because NRG1 and ErbB4 are susceptibility genes of schizophrenia, our findings might also help to explain the potential mechanism of emotional abnormality in schizophrenia.

UR - http://www.scopus.com/inward/record.url?scp=84925510404&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925510404&partnerID=8YFLogxK

U2 - 10.1038/npp.2014.274

DO - 10.1038/npp.2014.274

M3 - Article

VL - 40

SP - 974

EP - 986

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

SN - 0893-133X

IS - 4

ER -