Hippocampal fear engrams modulate ethanol-induced maladaptive contextual generalization in mice.
Hippocampal fear engrams modulate ethanol-induced maladaptive contextual generalization in mice.
复制标题
海马恐惧印迹调节小鼠乙醇诱导的适应不良情境泛化。
DOI：
10.1002/hipo.23463
复制
发表时间：
2022
期刊：
影响因子：
3.5
通讯作者：
Ramirez,Steve
中科院分区：
文献类型：
--
作者：
Cincotta,Christine;Ruesch,Evan;Senne,Ryan;Ramirez,Steve
酒精使用障碍（AUD）和同时发生的精神健康障碍的复合病理学引起了适应不良神经生物学过程的相互作用，其病因是难以捉摸的。在这里，我们设计了一种光遗传学策略，旨在挽救雄性c57 BL/6小鼠的适应不良的恐惧处理，这些小鼠经历了慢性乙醇给药和强迫禁欲范例。在第一个实验中，我们证实了乙醇暴露小鼠在恐惧条件反射和暴露于新环境期间，恐惧获得和适应不良的上下文泛化分别增强。在第二个实验中，使用活动依赖性泰特标签系统，我们用抑制性视蛋白标记背侧海马中由情境恐惧条件反射选择性激活的神经系综，以减轻乙醇暴露引起的行为功能障碍。我们发现，暴露于新环境期间的急性光遗传学扰动抑制了乙醇暴露小鼠的适应不良泛化。这些结果提供了进一步的证据，乙醇暴露和受损的恐惧记忆处理之间的关键联系，通过提供细胞和行为的见解，神经回路的基础AUD和适应不良的恐惧处理。
The compounding symptomatology of alcohol use disorder (AUD) and co‐occurring mental health disorders gives rise to interactions of maladaptive neurobiological processes, the etiology of which are elusive. Here, we devised an optogenetic strategy aimed at rescuing maladaptive fear processing in male c57BL/6 mice that underwent a chronic ethanol administration and forced abstinence paradigm. In the first experiment, we confirmed that fear acquisition and maladaptive contextual generalization was potentiated in ethanol‐exposed mice during fear conditioning and exposure to a novel environment, respectively. In the second experiment, using an activity‐dependent tet‐tag system, we labeled the neural ensemble selectively activated by contextual fear conditioning in the dorsal hippocampus with an inhibitory opsin to attenuate behavioral dysfunctions resulting from ethanol exposure. We found that acute optogenetic perturbations during exposure to a novel environment suppressed maladaptive generalization in ethanol‐exposed mice. These results provide further evidence for a crucial link between ethanol exposure and impaired fear memory processing by providing cellular and behavioral insights into the neural circuitry underlying AUD and maladaptive fear processing.