Background

In both rodents and humans, the basolateral amygdala (BLA) is essential for encoding and retrieving conditioned fear memories. Although the BLA is a putative storage site for these memories, recent evidence suggests that they become independent of the BLA with the passage of time.

Methods

We systematically examined the role for the BLA in the retrieval of recent (1 day) and remote (2 weeks) fear memory using optogenetic, electrophysiological, and calcium imaging methods in male and female Long-Evans rats. Critically, we used a behavioral design that permits within-subjects comparison of recent and remote memory at the same time point; freezing behavior served as the index of learned fear.

Results

We found that BLA c-Fos expression was similar after the retrieval of recent or remote fear memories. Extracellular single-unit recordings in awake, behaving animals revealed that single BLA neurons exhibit robust increases in spike firing to both recent and remote conditioned stimuli. Fiber photometry recordings revealed that these patterns of activity emerge from principal neurons. Consistent with these results, optogenetic inhibition of BLA principal neurons impaired conditioned freezing to both recent and remote conditioned stimuli. There were no sex differences in any of the measures or manipulations.

Conclusions

These data reveal that BLA neurons encode both recent and remote fear memories, suggesting substantial overlap in the allocation of temporally distinct events. This may underlie the broad generalization of fear memories across both space and time. Ultimately, these results provide evidence that the BLA is a long-term storage site for emotional memories.

中文翻译：

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基底外侧杏仁核近期和远期恐惧记忆的收敛编码

背景

在啮齿动物和人类中，基底外侧杏仁核 (BLA) 对于编码和检索条件性恐惧记忆至关重要。尽管 BLA 是这些记忆的假定存储站点，但最近的证据表明，随着时间的推移，它们会独立于 BLA。

方法

我们使用光遗传学、电生理学和钙成像方法在雄性和雌性 Long-Evans 大鼠中系统地检查了 BLA 在最近（1 天）和遥远（2 周）恐惧记忆检索中的作用。至关重要的是，我们使用了一种行为设计，允许在同一时间点对最近和遥远的记忆进行受试者内部比较；冻结行为作为习得性恐惧的指标。

结果

我们发现 BLA c-Fos 表达在检索最近或遥远的恐惧记忆后是相似的。在清醒的、有行为的动物中的细胞外单单元记录显示，单个 BLA 神经元在对最近和远程条件刺激的尖峰发射中表现出强劲的增加。纤维光度记录显示这些活动模式来自主要神经元。与这些结果一致，BLA 主要神经元的光遗传学抑制损害了对最近和远程条件刺激的条件冻结。在任何措施或操作中都没有性别差异。

结论

这些数据表明 BLA 神经元对近期和遥远的恐惧记忆进行编码，表明在时间上不同的事件分配中存在大量重叠。这可能是恐惧记忆在空间和时间上广泛概括的基础。最终，这些结果证明 BLA 是情感记忆的长期存储场所。