The mechanisms of fear attenuation Surprisingly little is known about how remote fearful memories are stored and attenuated. Khalaf et al. used independent fear memory attenuation paradigms, engram-based tagging techniques, and chemogenetic tools to alter neuronal activity (see the Perspective by Frankland and Josselyn). They found that a discrete subset of neurons within an ensemble is engaged during recall after memory attenuation, which correlated with fear reduction. Memory updating and extinction mechanisms thus likely coexist to make this happen. These findings support the notion that effective memory attenuation is mediated by a rewriting of the original memory trace of fear toward one of safety. Science, this issue p. 1239; see also p. 1186 During the attenuation of long-lasting fear memories, the original memory trace is reengaged toward safety. Whether fear attenuation is mediated by inhibition of the original memory trace of fear with a new memory trace of safety or by updating of the original fear trace toward safety has been a long-standing question in neuroscience and psychology alike. In particular, which of the two scenarios underlies the attenuation of remote (month-old) fear memories is completely unknown, despite the impetus to better understand this process against the backdrop of enduring traumata. We found—chemogenetically and in an engram-specific manner—that effective remote fear attenuation is accompanied by the reactivation of memory recall–induced neurons in the dentate gyrus and that the continued activity of these neurons is critical for fear reduction. This suggests that the original memory trace of fear actively contributes to remote fear attenuation.

中文翻译：

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回忆诱导神经元的重新激活有助于远程恐惧记忆衰减

恐惧减弱的机制 令人惊讶的是，关于遥远的恐惧记忆是如何存储和减弱的，我们知之甚少。哈拉夫等人。使用独立的恐惧记忆衰减范式、基于印迹的标记技术和化学遗传学工具来改变神经元活动（参见 Frankland 和 Josselyn 的观点）。他们发现，在记忆衰减后的回忆过程中，一个集合中的一个离散神经元子集会参与其中，这与恐惧减少有关。因此，内存更新和消亡机制可能共存以实现这一目标。这些发现支持这样一种观点，即有效的记忆衰减是通过将恐惧的原始记忆痕迹改写为安全性来介导的。科学，本期第 3 页。1239; 另见第 第1186期 原来的记忆痕迹被重新投入到安全中。恐惧减弱是通过用新的安全记忆痕迹抑制原始恐惧记忆痕迹来介导的，还是通过将原始恐惧痕迹更新为安全来介导的，这一直是神经科学和心理学等领域长期存在的问题。特别是，这两种情景中的哪一种是遥远（一个月大）恐惧记忆减弱的基础，这完全未知，尽管在持久创伤的背景下更好地理解这一过程的动力是完全未知的。我们发现——在化学遗传学上和以特定于印迹的方式——有效的远程恐惧减弱伴随着记忆回忆诱导的齿状回神经元的重新激活，并且这些神经元的持续活动对于减少恐惧至关重要。