Chronic activation of fear engrams induces extinction-like behavior in ethanol-exposed mice.
Chronic activation of fear engrams induces extinction-like behavior in ethanol-exposed mice.
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DOI：
10.1002/hipo.23263
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发表时间：
2021-01
期刊：
影响因子：
3.5
通讯作者：
Ramirez S
中科院分区：
文献类型：
--
作者：
Cincotta C;Murawski NJ;Grella SL;McKissick O;Doucette E;Ramirez S
酒精戒断直接影响大脑的压力和记忆系统，这可能是个体对持续药物和酒精寻求行为的易感性的基础。许多研究表明，强迫戒酒可能导致戒断，会损害啮齿动物与恐惧相关的记忆过程，如灭绝学习;然而，介导这些损伤的潜在神经回路仍然难以捉摸。在这里，我们测试了一种光遗传学策略，旨在减轻雄性c57 BL/6小鼠在暴露于酒精后的恐惧消退检索障碍（即，酒精）和强迫禁欲。在第一个实验中，与对照组相比，暴露于乙醇的小鼠在恐惧条件下的广泛行为消退训练受损。在第二个实验中，在背侧海马中处理上下文恐惧记忆的神经元集合被标记，并在乙醇暴露和对照小鼠的不同背景下重复地光遗传学重新激活。这些细胞的慢性激活导致对照组和乙醇暴露组小鼠的恐惧反应出现情境特异性的、类似预防的减少。这些发现表明，虽然乙醇会损害记忆的恢复，但光遗传学对恐惧记忆的操纵足以诱导恐惧反应的预防性减少。
Alcohol withdrawal directly impacts the brain’s stress and memory systems, which may underlie individual susceptibility to persistent drug and alcohol-seeking behaviors. Numerous studies demonstrate that forced alcohol abstinence, which may lead to withdrawal, can impair fear-related memory processes in rodents such as extinction learning; however, the underlying neural circuits mediating these impairments remain elusive. Here, we tested an optogenetic strategy aimed at mitigating fear extinction retrieval impairments in male c57BL/6 mice following exposure to alcohol (i.e., ethanol) and forced abstinence. In the first experiment, extensive behavioral extinction training in a fear-conditioned context was impaired in ethanol-exposed mice compared to controls. In the second experiment, neuronal ensembles processing a contextual fear memory in the dorsal hippocampus were tagged and optogenetically reactivated repeatedly in a distinct context in ethanol-exposed and control mice. Chronic activation of these cells resulted in a context-specific, extinction-like reduction in fear responses in both control and ethanol-exposed mice. These findings suggest that while ethanol can impair the retrieval an extinction memory, optogenetic manipulation of a fear engram is sufficient to induce an extinction-like reduction in fear responses.
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乙醇暴露对提示和上下文恐惧条件和灭绝的后果因青春期或成年期暴露时间而有所不同。
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