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Archival Report| Volume 87, ISSUE 10, P926-936, May 15, 2020

Erbin in Amygdala Parvalbumin-Positive Neurons Modulates Anxiety-like Behaviors

  • Author Footnotes
    1 Z-YL and LH contributed equally to this work.
    Zheng-Yi Luo
    Footnotes
    1 Z-YL and LH contributed equally to this work.
    Affiliations
    State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Collaborative Innovation Center for Brain Science, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
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  • Author Footnotes
    1 Z-YL and LH contributed equally to this work.
    Lang Huang
    Footnotes
    1 Z-YL and LH contributed equally to this work.
    Affiliations
    State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Collaborative Innovation Center for Brain Science, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
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  • Song Lin
    Affiliations
    State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Collaborative Innovation Center for Brain Science, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
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  • Ya-Nan Yin
    Affiliations
    State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Collaborative Innovation Center for Brain Science, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
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  • Wei Jie
    Affiliations
    State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Collaborative Innovation Center for Brain Science, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
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  • Neng-Yuan Hu
    Affiliations
    State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Collaborative Innovation Center for Brain Science, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
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  • Yu-Ying Hu
    Affiliations
    State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Collaborative Innovation Center for Brain Science, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
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  • Yan-Fei Guan
    Affiliations
    State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Collaborative Innovation Center for Brain Science, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
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  • Ji-Hong Liu
    Affiliations
    State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Collaborative Innovation Center for Brain Science, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
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  • Qiang-Long You
    Affiliations
    State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Collaborative Innovation Center for Brain Science, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
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  • Yi-Hua Chen
    Affiliations
    State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Collaborative Innovation Center for Brain Science, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
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  • Zhou-Cai Luo
    Affiliations
    State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Collaborative Innovation Center for Brain Science, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
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  • Sheng-Rong Zhang
    Affiliations
    State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Collaborative Innovation Center for Brain Science, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
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  • Xiao-Wen Li
    Affiliations
    State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Collaborative Innovation Center for Brain Science, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
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  • Jian-Ming Yang
    Affiliations
    State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Collaborative Innovation Center for Brain Science, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
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  • Yan-Mei Tao
    Affiliations
    Institute of Life Sciences, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, China
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  • Author Footnotes
    2 LM and T-MG contributed equally to this work.
    Lin Mei
    Footnotes
    2 LM and T-MG contributed equally to this work.
    Affiliations
    Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio
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  • Author Footnotes
    2 LM and T-MG contributed equally to this work.
    Tian-Ming Gao
    Correspondence
    Address correspondence to Tian-Ming Gao, M.D., Ph.D., State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
    Footnotes
    2 LM and T-MG contributed equally to this work.
    Affiliations
    State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Collaborative Innovation Center for Brain Science, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
    Search for articles by this author
  • Author Footnotes
    1 Z-YL and LH contributed equally to this work.
    2 LM and T-MG contributed equally to this work.
Published:November 01, 2019DOI:https://doi.org/10.1016/j.biopsych.2019.10.021

      Abstract

      Background

      Anxiety disorders are the most common psychiatric diseases, affecting 28% of people worldwide within their lifetime. The excitation-inhibition imbalance in the amygdala is thought to be an underlying pathological mechanism; however, the cellular and molecular control of amygdala excitation-inhibition balance is largely unknown.

      Methods

      By using mice expressing chemogenetic activator or inhibitor channel in amygdala parvalbumin (PV) neurons, Erbin mutant mice, and mice with Erbin specifically knocked down in amygdala PV neurons, we systematically investigated the role of amygdala PV neurons and Erbin expressed therein in the pathogenesis of anxiety disorders using the combined approaches of immunohistochemistry, electrophysiology, and behavior.

      Results

      In naïve mice, chemogenetic inhibition of PV neurons produced anxiogenic effects, suggesting an essential role in the regulation of anxiety. In stressed mice with anxiety, excitatory postsynaptic responses on amygdala PV neurons were selectively diminished, accompanied by a decreased expression of Erbin specifically in amygdala PV neurons. Remarkably, both Erbin mutant mice and amygdala PV–specific Erbin knockdown mice exhibited impaired excitatory postsynaptic responses on amygdala PV neurons and increased anxiety-like behaviors. Furthermore, chemogenetic activation of amygdala PV neurons normalized anxiety behaviors in amygdala PV–specific Erbin knockdown mice and stressed mice.

      Conclusions

      Together, these results demonstrate that Erbin in PV neurons is critical for maintaining the excitation-inhibition balance in the amygdala and reveal a novel pathophysiological mechanism for anxiety disorders.

      Keywords

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      • An Erbin Story: Amygdala Excitation-Inhibition Balance in Anxiety
        Biological PsychiatryVol. 87Issue 10
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          Anxiety disorders (with a lifetime prevalence of ∼30%) are associated with high personal and socioeconomic burden, while current treatments are inadequate because of the lack of clear understanding of the underlying mechanisms (1,2). The amygdala has long been implicated as a key emotional control circuit mediating anxiety. Particularly, the basolateral amygdala (BLA), which receives sensory information from thalamic and cortical inputs via the lateral amygdala, integrates and processes this information, relaying it to various output regions directly or via the central amygdala, to generate fear- and anxiety-related autonomic, endocrine, and behavioral responses to potential threats (2).
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