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

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33 Scopus citations

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 - Mar 2015

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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., Geng, F., Liu, F., Zhang, M., Liu, J. H., Li, X. W., Mei, L., & 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