Fear memory formation and recall are highly regulated processes, with the central amygdala (CeA) contributing to fear memory-related behaviors. We recently reported that a remote fear memory engram is resident in the anterior basolateral amygdala (aBLA). However, the extent to which downstream neurons in the CeA participate in this engram is unknown. We tested the hypothesis that CeA neurons activated during fear memory formation are reactivated during remote memory retrieval such that a CeA engram participates in remote fear memory recall and its associated behavior. Using contextual fear conditioning in TRAP2;Ai14 mice, we identified, by persistent Cre-dependent tdTomato expression (i.e., “TRAPing”), CeA neurons that were c-fos-activated during memory formation. Twenty-one days later, we quantified neurons activated during remote memory recall using Fos immunohistochemistry. Dual labeling was used to identify the subpopulation of CeA neurons that was both activated during memory formation and reactivated during recall. Compared with their context-conditioned (no shock) controls, fear-conditioned (electric shock) mice (n = 5/group) exhibited more robust fear memory-related behavior (freezing) as well as larger populations of activated (tdTomato⁺) and reactivated (dual-labeled) CeA neurons. Most neurons in both groups were mainly located in the capsular CeA subdivision (CeAC). Notably, however, only the size of the TRAPed population distributed throughout the CeA was significantly correlated with time spent freezing during remote fear memory recall. Our findings indicate that fear memory formation robustly activates CeA neurons and that a subset located mainly in the CeAC may contribute to both remote fear memory storage/retrieval and the resulting fear-like behavior.

中文翻译：

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杏仁核中央存在远程恐惧记忆印迹

恐惧记忆的形成和回忆是受到高度调控的过程，中央杏仁核（CeA）有助于恐惧记忆相关的行为。我们最近报道说，一个遥远的恐惧记忆印迹存在于前基底外侧杏仁核（aBLA）中。然而，CeA 下游神经元参与该印迹的程度尚不清楚。我们测试了这样的假设：在恐惧记忆形成过程中激活的 CeA 神经元在远程记忆检索过程中被重新激活，因此 CeA 印迹参与远程恐惧记忆回忆及其相关行为。在 TRAP2;Ai14 小鼠中使用情境恐惧调节，我们通过持续的 Cre 依赖性 tdTomato 表达（即“TRAPing”）识别出在记忆形成过程中被c-fos激活的 CeA 神经元。二十一天后，我们使用 Fos 免疫组织化学定量了远程记忆回忆过程中激活的神经元。双标记用于识别在记忆形成过程中被激活并在回忆过程中重新激活的 CeA 神经元亚群。与环境条件（无电击）对照组相比，恐惧条件（电击）小鼠（n = 5/组）表现出更强烈的恐惧记忆相关行为（冻结）以及更多的激活（tdTomato ⁺）和重新激活（双标记）CeA 神经元。两组的大多数神经元主要位于囊状 CeA 分区（CeAC）。然而值得注意的是，只有分布在整个 CeA 中的 TRAPed 群体的大小与远程恐惧记忆回忆期间冻结的时间显着相关。我们的研究结果表明，恐惧记忆的形成会强烈激活 CeA 神经元，并且主要位于 CeAC 中的一个子集可能有助于远程恐惧记忆存储/检索以及由此产生的恐惧样行为。