The lateral central nucleus of the amygdala (CeA_L) and the dorsolateral bed nucleus of the stria terminalis (BNST_DL) coordinate the expression of shorter- and longer-lasting fears, respectively. Less is known about how these structures communicate with each other during fear acquisition. One pathway, from the CeA_L to the BNST_DL, is thought to communicate via corticotropin-releasing factor (CRF), but studies have yet to examine its function in fear learning and memory. Thus, we developed an adeno-associated viral-based strategy to selectively target CRF neurons with the optogenetic silencer archaerhodopsin tp009 (CRF-ArchT) to examine the role of CeA_L CRF neurons and projections to the BNST_DL during the acquisition of contextual fear. Expression of our CRF-ArchT vector injected into the amygdala was restricted to CeA_L CRF neurons. Furthermore, CRF axonal projections from the CeA_L clustered around BNST_DL CRF cells. Optogenetic silencing of CeA_L CRF neurons during contextual fear acquisition disrupted retention test freezing 24 h later, but only at later time points (>6 min) during testing. Silencing CeA_L CRF projections in the BNST_DL during contextual fear acquisition produced a similar effect. Baseline contextual freezing, the rate of fear acquisition, freezing in an alternate context after conditioning and responsivity to foot shock were unaffected by optogenetic silencing. Our results highlight how CeA_L CRF neurons and projections to the BNST_DL consolidate longer-lasting components of a fear memory. Our findings have implications for understanding how discrete amygdalar CRF pathways modulate longer-lasting fear in anxiety- and trauma-related disorders.

中文翻译：

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从中央杏仁核到纹状体终末床核的促肾上腺皮质激素释放因子途径的光遗传学沉默破坏了持续的恐惧感。

杏仁核的外侧中央核（CeA _L）和纹状体的背外侧床核（BNST _DL）分别协调了持续时间较短和持续时间较长的恐惧。关于这些结构在恐惧获取过程中如何相互沟通的了解还很少。人们认为，从CeA _L到BNST _DL的一种途径是通过促肾上腺皮质激素释放因子（CRF）进行交流，但是尚未有研究检查其在恐惧学习和记忆中的作用。因此，我们开发了一种基于腺相关病毒的策略，用光遗传沉默子古细菌视紫红质tp009（CRF-ArchT）选择性靶向CRF神经元，以检查CeA _L CRF神经元的作用以及对BNST _DL的预测在获得上下文恐惧的过程中。注入杏仁核的我们的CRF-ArchT载体的表达仅限于CeA _L CRF神经元。此外，来自CeA _L的CRF轴突投影聚集在BNST _DL CRF细胞周围。CeA _L CRF神经元的光遗传沉默在获得背景恐惧感时破坏了24小时后冻结的保留测试，但仅在测试过程中的较晚时间点（> 6分钟）中断。沉默杏仁_大号CRF突起在BNST _DL在上下文恐惧中获得类似的效果。基线情境冻结，恐惧恐惧发生率，调理后在另一情境中冻结以及对足部电击的反应性不受光遗传学沉默的影响。我们的结果强调了CeA _L CRF神经元和BNST _DL的投射如何巩固恐惧记忆的持久成分。我们的发现对理解离散的杏仁核CRF通路如何调节焦虑和创伤相关疾病中的长期恐惧具有重要意义。