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腹侧海马中间神经元控制情境关联的消退和复发。

Ventral hippocampal interneurons govern extinction and relapse of contextual associations.

作者信息

Lacagnina Anthony F, Dong Tri N, Iyer Rasika R, Khan Saqib, Mohamed Mazen K, Clem Roger L

出版信息

bioRxiv. 2023 Nov 28:2023.11.28.568835. doi: 10.1101/2023.11.28.568835.

DOI:10.1101/2023.11.28.568835
PMID:38077077
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10705382/
Abstract

Contextual associations are critical for survival but must be extinguished when new conditions render them nonproductive. By most accounts, extinction forms a new memory that competes with the original association for control over behavior, but the mechanisms underlying this competition remain largely enigmatic. Here we find the retrieval of contextual fear conditioning and extinction yield contrasting patterns of activity in prefrontal cortex and ventral hippocampus. Within ventral CA1, activation of somatostatin-expressing interneurons (SST-INs) occurs preferentially during extinction retrieval and correlates with differences in input synaptic transmission. Optogenetic manipulation of these cells but not parvalbumin interneurons (PV-INs) elicits bidirectional changes in fear expression following extinction, and the ability of SST-INs to gate fear is specific to the context in which extinction was acquired. A similar pattern of results was obtained following reward-based extinction. These data show that ventral hippocampal SST-INs are critical for extinguishing prior associations and thereby gate relapse of both aversive and appetitive responses.

摘要

情境关联对生存至关重要,但当新情况使其变得无效时,必须予以消除。多数观点认为,消退形成一种新记忆,与原始关联竞争对行为的控制,但这种竞争背后的机制在很大程度上仍不明确。在这里,我们发现情境恐惧条件反射和消退的检索在前额叶皮层和腹侧海马体中产生了相反的活动模式。在腹侧CA1内,表达生长抑素的中间神经元(SST-INs)的激活在消退检索期间优先发生,并且与输入突触传递的差异相关。对这些细胞而非小白蛋白中间神经元(PV-INs)进行光遗传学操作,会在消退后引起恐惧表达的双向变化,并且SST-INs调节恐惧的能力特定于获得消退的情境。在基于奖励的消退后也获得了类似的结果模式。这些数据表明,腹侧海马体SST-INs对于消除先前的关联至关重要,从而调节厌恶和食欲反应的复发。

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