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

Biological psychiatry 2020 May 15

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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. 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. 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. 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. Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Citation

Zheng-Yi Luo, Lang Huang, Song Lin, Ya-Nan Yin, Wei Jie, Neng-Yuan Hu, Yu-Ying Hu, Yan-Fei Guan, Ji-Hong Liu, Qiang-Long You, Yi-Hua Chen, Zhou-Cai Luo, Sheng-Rong Zhang, Xiao-Wen Li, Jian-Ming Yang, Yan-Mei Tao, Lin Mei, Tian-Ming Gao. Erbin in Amygdala Parvalbumin-Positive Neurons Modulates Anxiety-like Behaviors. Biological psychiatry. 2020 May 15;87(10):926-936