Differential recruitment of brain circuits during fear extinction in non-stressed compared to stress resilient animals.
Differential recruitment of brain circuits during fear extinction in non-stressed compared to stress resilient animals.
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DOI：
10.1038/s41598-023-50830-w
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发表时间：
2024-01-25
影响因子：
4.6
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中科院分区：
文献类型：
--
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创伤后应激障碍(PTSD)中功能失调的恐惧反应可能部分是因为无法有效地消除由创伤相关线索引发的恐惧反应。然而，只有一部分暴露在创伤应激下的人会患上创伤后应激障碍。因此，在个体差异的动物模型中研究恐惧消退缺陷，可能有助于识别潜在的神经基础，即对压力影响的脆弱性或恢复力。我们使用了一个社会失败的大鼠模型，在这个模型中，大鼠被分成被动和主动应对的大鼠。在之前的工作中，我们发现被动应对的大鼠表现出社交互动的中断，而主动应对的大鼠没有表现出与对照组不同的行为，这表明它们的弹性。在这里，成年雄性大鼠暴露在7天的社会失败中，使用情境恐惧和与行为学相关的恐惧测试来测试恐惧消退、消亡保持和保持的持久性。被动应对的大鼠在先前熄灭的环境中表现出更高的冰冻程度。对特定脑区CFos表达细胞的分析表明，在海马背侧亚区内高度相关，而被动应对大鼠的背侧海马CA1与杏仁核中央和基底外侧亚区之间高度相关。重要的是，尽管对照组和积极应对的大鼠表现出相似的行为消亡水平，但激活的结构之间几乎没有相似之处，这表明，应对慢性社会失败的压力弹性涉及大脑回路的适应性差异招募，以成功消除恐惧记忆。
Dysfunctional fear responses in post-traumatic stress disorder (PTSD) may be partly explained by an inability to effectively extinguish fear responses elicited by trauma-related cues. However, only a subset of individuals exposed to traumatic stress develop PTSD. Therefore, studying fear extinction deficits in animal models of individual differences could help identify neural substrates underlying vulnerability or resilience to the effects of stress. We used a rat model of social defeat in which rats segregate into passively and actively coping rats. In previous work, we showed that passively coping rats exhibit disruptions in social interaction whereas actively coping rats do not display behaviors differently from controls, indicating their resilience. Here, adult male rats exposed to 7 days of social defeat were tested for fear extinction, retention of extinction, and persistence of retention using contextual fear and ethologically-relevant fear tests. Passively coping rats exhibited elevated freezing in response to the previously extinguished context. Analyses of cFos expressing cells across select brain regions showed high correlations within dorsal hippocampal subregions, while passively coping rats had high correlations between the dorsal hippocampus CA1 and the central and basolateral subregions of the amygdala. Importantly, although control and actively coping rats showed similar levels of behavioral extinction, there was little similarity between activated structures, suggesting stress resilience in response to chronic social defeat involves an adaptive differential recruitment of brain circuits to successfully extinguish fear memories.
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影响因子：
4.6
作者：
Laine MA;Sokolowska E;Dudek M;Callan SA;Hyytiä P;Hovatta I
通讯作者：
Hovatta I
影响因子：
2.4
作者：
Nakamura H;Katayama Y;Kawakami Y
通讯作者：
Kawakami Y
影响因子：
3.3
作者：
Blume SR;Nam H;Luz S;Bangasser DA;Bhatnagar S
通讯作者：
Bhatnagar S
影响因子：
3.4
作者：
Kreutzmann, Judith C.;Jovanovic, Tanja;Fendt, Markus
通讯作者：
Fendt, Markus
影响因子：
16.6
作者：
Corbett, Brian F.;Luz, Sandra;Bhatnagar, Seema
通讯作者：
Bhatnagar, Seema