Erbin in Amygdala Parvalbumin-Positive Neurons Modulates Anxiety-like Behaviors
Erbin in Amygdala Parvalbumin-Positive Neurons Modulates Anxiety-like Behaviors
复制标题
杏仁核小白蛋白阳性神经元中的 Erbin 调节焦虑样行为。
DOI：
10.1016/j.biopsych.2019.10.021
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发表时间：
2020-05-15
影响因子：
10.6
通讯作者：
Gao, Tian-Ming
中科院分区：
文献类型：
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作者：
Luo, Zheng-Yi;Huang, Lang;Gao, Tian-Ming
背景：焦虑症是最常见的精神疾病，影响全世界 28% 的人一生。杏仁核的兴奋-抑制失衡被认为是潜在的病理机制。然而，杏仁核兴奋-抑制平衡的细胞和分子控制在很大程度上是未知的。方法：通过使用在杏仁核小白蛋白（PV）神经元中表达化学遗传学激活剂或抑制剂通道的小鼠、Erbin突变小鼠和在杏仁核PV神经元中特异性敲除Erbin的小鼠，我们系统地研究了杏仁核PV神经元中Erbin的作用。 使用免疫组织化学、电生理学和行为相结合的方法，研究了杏仁核PV神经元和Erbin在焦虑症发病机制中的表达。结果：在幼鼠中，PV神经元的化学遗传学抑制产生了致焦虑作用，表明在焦虑调节中发挥着重要作用。在患有焦虑症的应激小鼠中，杏仁核 PV 神经元的兴奋性突触后反应选择性减弱，同时伴随着杏仁核 PV 神经元中 Erbin 表达的降低。值得注意的是，Erbin 突变小鼠和杏仁核 PV 特异性 Erbin 敲除小鼠均表现出杏仁核 PV 神经元的兴奋性突触后反应受损，并增加了焦虑样行为。此外，杏仁核 PV 神经元的化学遗传学激活使杏仁核 PV 特异性 Erbin 敲低小鼠和应激小鼠的焦虑行为正常化。结论：总的来说，这些结果表明 PV 神经元中的 Erbin 对于维持杏仁核的兴奋-抑制平衡至关重要，并揭示了焦虑症的一种新的病理生理机制。
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 naive 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.