Amygdala NRG1-ErbB4 Is Critical for the Modulation of Anxiety-Like Behaviors
Amygdala NRG1-ErbB4 Is Critical for the Modulation of Anxiety-Like Behaviors
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杏仁核 NRG1-ErbB4 对于调节焦虑样行为至关重要。
DOI：
10.1038/npp.2014.274
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发表时间：
2015-03-01
影响因子：
7.6
通讯作者：
Gao, Tian-Ming
中科院分区：
文献类型：
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作者：
Bi, Lin-Lin;Sun, Xiang-Dong;Gao, Tian-Ming
焦虑症与精神疾病的病理生理学有关，包括严重的抑郁症、药物滥用和精神分裂症。杏仁核对于焦虑的表现和调节很重要。然而，人们对控制杏仁核抑制活动的机制知之甚少，杏仁核抑制活动与焦虑有关。我们发现，杏仁基底外侧核(BLA)中唯一的自主受体ErbB4几乎全部在GABA能神经元中表达。BLA内源性NRG1ErbB4信号通路可调节焦虑样行为和GABA释放，但对谷氨酸能传递无影响。将NRG1注入高焦虑小鼠的BLA，可减轻其焦虑，增强GABA能神经传递。此外，外源性NRG1还对应激小鼠产生了缓解焦虑的作用。综上所述，这些观察表明，NRG1 ErbB4信号对于维持杏仁核中的GABA能活性至关重要，从而对调节焦虑样行为至关重要。由于NRG1和ErbB4是精神分裂症的易感基因，我们的发现也可能有助于解释精神分裂症情绪异常的潜在机制。
Anxiety disorder is related to the pathophysiology of psychiatric diseases, including major depression, substance abuse, and schizophrenia. The amygdala is important for manifestation and modulation of anxiety. However, relatively little is known regarding the mechanisms that control the amygdala inhibitory activity that is involved in anxiety. We found that almost all ErbB4, which is the only autonomous receptor of neuregulin 1 (NRG1) in the basolateral amygdala (BLA), was expressed in GABAergic neurons. Endogenous NRG1 ErbB4 signaling pathway in the BLA could modulate anxiety-like behaviors and GABA release, whereas it had no effect on glutamatergic transmission. The administration of NRG1 into the BLA of high-anxiety mice alleviated their anxiety and enhanced GABAergic neurotransmission. Moreover, exogenous NRG1 also produced an anxiolytic effect in the stressed mice. Together, these observations indicated that NRG1 ErbB4 signaling is critical to maintaining GABAergic activity in the amygdala and thus to modulating anxiety-like behaviors. Because NRG1 and ErbB4 are susceptibility genes of schizophrenia, our findings might also help to explain the potential mechanism of emotional abnormality in schizophrenia.