Reactivation of recall-induced neurons contributes to remote fear memory attenuation

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Science  15 Jun 2018:
Vol. 360, Issue 6394, pp. 1239-1242
DOI: 10.1126/science.aas9875

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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


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.

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