The occurrence of major depressive disorder (MDD) has been linked to an increased vulnerability to stress. The basolateral amygdala (BLA) is one of the critical brain areas that involved in the regulation of pathological reactivity to stress. Increasing evidence indicates that the EphB2 receptor (EphB2) plays a critical role in neuropsychiatric disorders, such as Alzheimer's disease, pain and anxiety. However, whether the EphB2 in the BLA is involved in stress vulnerability is unclear. Here, we identified EphB2 in the BLA as a key regulator contributed to the modulation of stress vulnerability in adult mice. We found that the expression of EphB2 in the BLA was significantly increased in the animal model induced by chronic social stress. Knockdown of EphB2 in the BLA produced antidepressant-like behavioral effects, whereas activation of EphB2 in the BLA increased the susceptibility to subthreshold social defeat stress. Furthermore, we demonstrated that the role of EphB2 in the stress vulnerability was mediated by modulating NMDA receptors, since the knockdown of EphB2 in the BLA prevented not only the increase in the amplitudes of both the miniature and the evoked NMDAR-mediated EPSC, but also the enhancement of surface expression of NMDARs in the defeated mice. Taken together, these results suggest that EphB2 in the BLA is a critical factor contributes to the vulnerability to stress, which may be a potential target for the treatment of depression.

中文翻译：

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EphB2在基底外侧杏仁核中的激活通过增加NMDA依赖性突触功能来促进小鼠的应激易感性。

重度抑郁症（MDD）的发生与压力增加有关。基底外侧杏仁核（BLA）是参与调节对压力的病理反应性的关键脑区之一。越来越多的证据表明，EphB2受体（EphB2）在神经精神疾病如阿尔茨海默氏病，疼痛和焦虑症中起关键作用。但是，尚不清楚BLA中的EphB2是否与应激易感性有关。在这里，我们确定了BLA中的EphB2是调节成年小鼠应激脆弱性的关键调节因子。我们发现，在慢性社会应激诱导的动物模型中，BLA中EphB2的表达显着增加。在BLA中敲除EphB2会产生类似抗抑郁药的行为效果，而BLA中EphB2的激活增加了对低于阈值的社会失败压力的敏感性。此外，我们证明了EphB2在应激脆弱性中的作用是通过调节NMDA受体来介导的，因为在BLA中EphB2的敲除不仅阻止了微型和诱发的NMDAR介导的EPSC振幅的增加，而且还阻止了击败小鼠时NMDAR表面表达的增强。综上所述，这些结果表明，BLA中的EphB2是导致压力脆弱性的关键因素，这可能是治疗抑郁症的潜在目标。因为在BLA中EphB2的敲低不仅阻止了缩微的和诱发的NMDAR介导的EPSC振幅的增加，而且还阻止了失败小鼠的NMDAR表面表达的增强。综上所述，这些结果表明，BLA中的EphB2是导致压力脆弱性的关键因素，这可能是治疗抑郁症的潜在目标。因为在BLA中EphB2的敲低不仅阻止了缩微的和诱发的NMDAR介导的EPSC振幅的增加，而且还阻止了失败小鼠的NMDAR表面表达的增强。综上所述，这些结果表明，BLA中的EphB2是导致压力脆弱性的关键因素，这可能是治疗抑郁症的潜在目标。