A Central Extended Amygdala Circuit That Modulates Anxiety
A Central Extended Amygdala Circuit That Modulates Anxiety
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DOI：
10.1523/jneurosci.0705-18.2018
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发表时间：
2018-06-13
影响因子：
5.3
通讯作者：
Li, Bo
中科院分区：
文献类型：
--
作者：
Ahrens, Sandra;Wu, Melody V.;Li, Bo
杏仁核和终纹床核（BNST）都与焦虑症的适应不良焦虑特征有关。然而，潜在的电路和细胞机制仍然难以捉摸。在这里，我们发现，在表达生长抑素（SOM（+））的神经元中Erbb 4基因缺陷的小鼠表现出高度的焦虑，这在高架十字迷宫测试和旷场测试中得到了测量，这两种测试通常用于评估啮齿动物的焦虑相关行为。利用电生理学、分子、遗传学和药理学技术的结合，我们证明突变小鼠的异常焦虑是由中央杏仁核（CeA）中SOM（+）神经元的兴奋性突触输入增强以及BNST中下游SOM（+）神经元的抑制减少引起的。值得注意的是，我们的研究结果表明，SOM（+）CeA神经元中强啡肽信号的增加介导了对SOM（+）BNST神经元抑制的矛盾减少，并且随之而来的SOM（+）BNST神经元活性的增强对于驱动升高的焦虑是必要的，也是足够的。最后，我们发现，在Erbb 4突变小鼠的CeA-BNST回路中，焦虑和相关的突触功能障碍以及强啡肽信号的增加可以通过野生型小鼠的应激来重现。总之，我们的研究结果解开了以前未知的电路和中央扩展杏仁核的细胞过程，可以导致适应不良的焦虑。
Both the amygdala and the bed nucleus of the stria terminalis (BNST) have been implicated in maladaptive anxiety characteristics of anxiety disorders. However, the underlying circuit and cellular mechanisms have remained elusive. Here we show that mice with Erbb4 gene deficiency in somatostatin-expressing (SOM (+)) neurons exhibit heightened anxiety as measured in the elevated plus maze test and the open field test, two assays commonlyused to assess anxiety-related behaviors in rodents. Using a combination of electrophysiological, molecular, genetic, and pharmacological techniques, we demonstrate that the abnormal anxiety in the mutant mice is caused by enhanced excitatory synaptic inputs onto SOM (+) neurons in the central amygdala (CeA), and the resulting reduction in inhibition onto downstream SOM (+) neurons in the BNST. Notably, our results indicate that an increase in dynorphin signaling in SOM (+) CeA neurons mediates the paradoxical reduction in inhibition onto SOM (+) BNST neurons, and that the consequent enhanced activity of SOM (+) BNST neurons is both necessary for and sufficient to drive the elevated anxiety. Finally, we show that the elevated anxiety and the associated synaptic dysfunctions and increased dynorphin signaling in the CeA-BNST circuit of the Erbb4 mutant mice can be recapitulated by stress in wild-type mice. Together, our results unravel previously unknown circuit and cellular processes in the central extended amygdala that can cause maladaptive anxiety.