Distinct hippocampal engrams control extinction and relapse of fear memory
Distinct hippocampal engrams control extinction and relapse of fear memory
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DOI：
10.1038/s41593-019-0361-z
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发表时间：
2019-05-01
影响因子：
25
通讯作者：
Drew, Michael R.
中科院分区：
文献类型：
--
作者：
Lacagnina, Anthony F.;Brockway, Emma T.;Drew, Michael R.
习得性恐惧通常在消退后复发，这表明消退训练产生了一种与原始恐惧记忆共存的新记忆;然而，控制竞争性恐惧和消退记忆表达的机制仍不清楚。我们使用活动依赖的神经标记来研究齿状回中恐惧和灭绝记忆的表征。我们证明，灭绝训练抑制再激活的上下文恐惧印迹细胞，同时激活第二个合奏，一个假定的灭绝印迹。在消退训练期间活跃的神经元的光遗传抑制增加了消退训练后的恐惧，而在恐惧训练期间活跃的沉默神经元减少了恐惧的自发恢复。光遗传刺激恐惧获得神经元增加恐惧，而刺激灭绝神经元抑制恐惧，防止自发恢复。我们的研究结果表明，海马体产生的恐惧灭绝表示和海马体之间的相互作用的恐惧和灭绝表示管辖灭绝后的抑制和复发的恐惧。
Learned fear often relapses after extinction, suggesting that extinction training generates a new memory that coexists with the original fear memory; however, the mechanisms governing the expression of competing fear and extinction memories remain unclear. We used activity-dependent neural tagging to investigate representations of fear and extinction memories in the dentate gyrus. We demonstrate that extinction training suppresses reactivation of contextual fear engram cells while activating a second ensemble, a putative extinction engram. Optogenetic inhibition of neurons that were active during extinction training increased fear after extinction training, whereas silencing neurons that were active during fear training reduced spontaneous recovery of fear. Optogenetic stimulation of fear acquisition neurons increased fear, while stimulation of extinction neurons suppressed fear and prevented spontaneous recovery. Our results indicate that the hippocampus generates a fear extinction representation and that interactions between hippocampal fear and extinction representations govern the suppression and relapse of fear after extinction.