Abstract：
Having experienced stress during sensitive periods of brain development strongly influences how individuals cope with later stress. Some are prone to develop anxiety or depression, while others appear resilient. The as-yet-unknown mechanisms underlying these differences may lie in how genes and environmental stress interact to shape the circuits that control emotions. Here, we investigated the role of the habenulo-interpeduncular system (HIPS), a critical node in reward circuits, in early stress-induced anxiety in mice. We found that habenular and IPN components characterized by the expression of Otx2 are synaptically connected and particularly sensitive to chronic stress (CS) during the peripubertal period. Stress-induced peripubertal activation of this HIPS subcircuit elicits both HIPS hypersensitivity to later stress and susceptibility to develop anxiety. We also show that HIPS silencing through conditional Otx2 knockout counteracts these effects of stress. Together, these results demonstrate that a genetic factor, Otx2, and stress interact during the peripubertal period to shape the stress sensitivity of the HIPS, which is shown to be a key modulator of susceptibility or resilience to develop anxiety.
摘要：
在大脑发育的敏感时期经历过压力会强烈影响个人如何应对以后的压力。有些人容易产生焦虑或抑郁，而其他人则显得有弹性。这些差异背后的未知机制可能在于基因和环境压力如何相互作用以形成控制情绪的回路。这里,我们研究了habenulo-peducular系统（HIPS）的作用，奖励电路中的关键节点，在小鼠早期应激诱导的焦虑中。我们发现，以Otx2表达为特征的in子和IPN成分在青春期期间是突触连接的，并且对慢性应激（CS）特别敏感。这种HIPS子回路的压力引起的青春期激活会引起HIPS对后期压力的敏感性和对焦虑的敏感性。我们还表明，通过条件Otx2敲除的HIPS沉默可以抵消压力的这些影响。一起,这些结果表明，遗传因素，Otx2和压力在青春期期间相互作用以形成HIPS的压力敏感性，这被证明是发展焦虑的易感性或韧性的关键调节剂。
