The insular cortex, anatomically close to amygdala, is also an integrative hub for sensory, emotional and cognitive function. Growing body of evidences suggest that alterations in insular structure and function have also been implicated in anxiety disorders. However, the reciprocal connections and precise subdivision of insular cortex involved in anxiety activities remains mechanistically unclear. In the present study, using anterograde and retrograde tracing methods, we verified that the anterior (AIa) but not posterior (AIp) agranular insular cortex is a major source of projections to the amygdala. Consistently, excitotoxic lesions only in AIa induced the anxiolytic behaviors and impaired fear memory. Using optogenetics methods, we found that selectively photoactivation of AIa GABAergic neurons remarkably promoted cued fear extinction and relieved anxiety in PSTD mice model. Finally, the participation of AIa in the storage of learned fear is also supported by the abolished LTP after fear conditioning and decreased the cued freezing using protein synthesis inhibitor immediately following training. Our results underscore the importance of AIa in fear and anxiety behavior and suggest that the AIa might share functions and interaction with amygdala in in anxiety related disorders.

中文翻译：

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粒状前小岛皮层在恐惧和焦虑调节中的作用。

在解剖学上接近杏仁核的岛状皮层也是感觉，情感和认知功能的综合枢纽。越来越多的证据表明，岛状结构和功能的改变也与焦虑症有关。但是，参与焦虑活动的岛状皮层的相互关系和精确细分在机械上仍不清楚。在本研究中，使用顺行和逆行追踪方法，我们验证了前（AIa）而非后（AIp）的非颗粒状岛状皮质是杏仁核投射的主要来源。一致地，仅在Ala中的兴奋性毒性损害诱导了抗焦虑行为并损害了恐惧记忆。使用光遗传学方法，我们发现在PSTD小鼠模型中，对AIa GABA能神经元的选择性光激活显着促进了暗示的恐惧消退并减轻了焦虑。最后，恐惧调节后取消的LTP还支持了AIa参与所学恐惧的存储，并在训练后立即使用蛋白质合成抑制剂降低了提示的冻结。我们的结果强调了AIa在恐惧和焦虑行为中的重要性，并表明在与焦虑相关的疾病中，AIa可能与杏仁核具有共同的功能和相互作用。