Geng Fei, Zhang Jie, Wu Jian-Lin, Zou Wen-Jun, Liang Zhi-Ping, Bi Lin-Lin, Liu Ji-Hong, Kong Ying, Huang Chu-Qiang, Li Xiao-Wen, Yang Jian-Ming, Gao Tian-Ming
State Key Laboratory of Organ Failure Research, Key Laboratory of Psychiatric Disorders of Guangdong Province, Collaborative Innovation Center for Brain Science, Department of Neurobiology, Southern Medical University, Guangzhou 510515, China.
State Key Laboratory of Organ Failure Research, Key Laboratory of Psychiatric Disorders of Guangdong Province, Collaborative Innovation Center for Brain Science, Department of Neurobiology, Southern Medical University, Guangzhou 510515, China.
Neuroscience. 2016 Aug 4;329:182-92. doi: 10.1016/j.neuroscience.2016.05.018. Epub 2016 May 14.
The bed nucleus of the stria terminalis (BNST), a nucleus defined as part of the extended amygdala, is involved in the expression of anxiety disorders. However, the regulatory mechanisms of BNST inhibitory activity that is involved in anxiety are unknown. Here, we showed that blocking neuregulin 1 (NRG1)-ErbB4 signaling in the BNST of mice, by either neutralizing endogenous NRG1 with ecto-Erbb4 or antagonizing the ErbB4 receptor with its specific inhibitor, produced anxiogenic responses. Interestingly, application of exogenous NRG1 into the BNST induced no anxiolytic effects, suggesting saturating activity of endogenous NRG1. While infusion of the GABAA receptor antagonist bicuculline into the BNST also led to anxiety-related behaviors, it did not worsen the anxiogenic effects produced by blocking NRG1-ErbB4 signaling, suggesting possible involvement of GABAergic neurotransmission. Further, in vitro electrophysiological recordings showed that BNST NRG1-ErbB4 signaling regulated the presynaptic GABA release. Together, these results suggest that NRG1-ErbB4 signaling in the BNST may play an important role in regulating anxiety-like behaviors.
终纹床核（BNST）是一个被定义为扩展杏仁核一部分的核团，参与焦虑症的表现。然而，参与焦虑的BNST抑制性活动的调节机制尚不清楚。在这里，我们表明，通过用胞外Erbb4中和内源性NRG1或用其特异性抑制剂拮抗ErbB4受体来阻断小鼠BNST中的神经调节蛋白1（NRG1）-ErbB4信号传导，会产生致焦虑反应。有趣的是，将外源性NRG1应用于BNST并未产生抗焦虑作用，这表明内源性NRG1具有饱和活性。虽然将GABAA受体拮抗剂荷包牡丹碱注入BNST也会导致与焦虑相关的行为，但它并没有加剧阻断NRG1-ErbB4信号传导所产生的致焦虑作用，这表明可能涉及GABA能神经传递。此外，体外电生理记录表明，BNST中的NRG1-ErbB4信号传导调节突触前GABA的释放。总之，这些结果表明，BNST中的NRG1-ErbB4信号传导可能在调节焦虑样行为中起重要作用。
