Anterior basolateral amygdala neurons comprise a remote fear memory engram.
Anterior basolateral amygdala neurons comprise a remote fear memory engram.
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DOI：
10.3389/fncir.2023.1167825
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发表时间：
2023
影响因子：
3.5
通讯作者：
Toney, Glenn M.
中科院分区：
文献类型：
--
作者：
Hammack, Robert J.;Fischer, Victoria E.;Andrade, Mary Ann;Toney, Glenn M.
威胁性的环境线索通常会产生持久的恐惧记忆，但这些记忆是如何形成和储存的仍在积极研究中。最近的恐惧记忆的回忆被认为反映了在记忆形成期间激活的多个脑区域中的神经元的重新激活，这表明解剖学上分布和互连的神经元集合包括恐惧记忆痕迹。然而，在长期恐惧记忆回忆过程中，解剖学上特异性的激活-再激活痕迹在多大程度上持续存在，在很大程度上仍未被探索。我们假设，前基底外侧杏仁核（aBLA）的主要神经元，编码负价，在远程恐惧记忆回忆驱动恐惧行为的急性再激活。使用TRAP 2和A114小鼠的成年后代，持续tdTomato表达用于“TRAP”在情境恐惧条件反射（电击）或仅情境条件反射（无电击）期间经历Fos激活的aBLA神经元（n = 5/组）。三周后，将小鼠再次暴露于相同的背景线索以进行远程记忆回忆，然后处死用于Fos免疫组织化学。TRAPed（tdTomato +），Fos +，和重新激活（双标记）的神经元合奏更大的恐惧比上下文条件的小鼠，与中间的子区域和中间/尾部背内侧象限的aBLA显示所有三个合奏人口的最大密度。而tdTomato +合奏的背景和恐惧组中占主导地位，冻结行为在远程记忆回忆与合奏的大小在任何一组。我们的结论是，虽然一个aBLA-inclusive恐惧记忆的痕迹形式，并持续在一个遥远的时间点，可塑性影响的电生理反应的痕迹神经元，而不是他们的人口规模，编码恐惧记忆和驱动器的长期恐惧记忆回忆的行为表现。
Threatening environmental cues often generate enduring fear memories, but how these are formed and stored remains actively investigated. Recall of a recent fear memory is thought to reflect reactivation of neurons, in multiple brain regions, activated during memory formation, indicating that anatomically distributed and interconnected neuronal ensembles comprise fear memory engrams. The extent to which anatomically specific activation-reactivation engrams persist during long-term fear memory recall, however, remains largely unexplored. We hypothesized that principal neurons in the anterior basolateral amygdala (aBLA), which encode negative valence, acutely reactivate during remote fear memory recall to drive fear behavior. Using adult offspring of TRAP2 and Ai14 mice, persistent tdTomato expression was used to “TRAP” aBLA neurons that underwent Fos-activation during contextual fear conditioning (electric shocks) or context only conditioning (no shocks) (n = 5/group). Three weeks later, mice were re-exposed to the same context cues for remote memory recall, then sacrificed for Fos immunohistochemistry. TRAPed (tdTomato +), Fos +, and reactivated (double-labeled) neuronal ensembles were larger in fear- than context-conditioned mice, with the middle sub-region and middle/caudal dorsomedial quadrants of aBLA displaying the greatest densities of all three ensemble populations. Whereas tdTomato + ensembles were dominantly glutamatergic in context and fear groups, freezing behavior during remote memory recall was not correlated with ensemble sizes in either group. We conclude that although an aBLA-inclusive fear memory engram forms and persists at a remote time point, plasticity impacting electrophysiological responses of engram neurons, not their population size, encodes fear memory and drives behavioral manifestations of long-term fear memory recall.
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