Anterior Cingulate Cortex to Ventral Hippocampus Circuit Mediates Contextual Fear Generalization
Anterior Cingulate Cortex to Ventral Hippocampus Circuit Mediates Contextual Fear Generalization
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前扣带皮层到腹侧海马回路介导情境恐惧泛化
DOI：
10.1523/jneurosci.2739-18.2019
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发表时间：
2019-07-17
影响因子：
5.3
通讯作者：
Zhu, Dong-Ya
中科院分区：
文献类型：
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作者：
Bian, Xin-Lan;Qin, Cheng;Zhu, Dong-Ya
随着时间的推移，情境恐惧记忆变得不那么特定于情境，这种现象被称为情境恐惧泛化。背景恐惧记忆的过度泛化是创伤后应激障碍（PTSD）的核心症状，但泛化背后的电路机制尚不清楚。我们在这里表明，从前扣带皮层（ACC）腹侧海马（vHPC）的神经投射介导的上下文恐惧泛化的雄性小鼠。在一个新的背景下，在一个遥远的时间点检索上下文恐惧激活细胞在ACC和vHPC，如显着增加C-fos+细胞。使用化学遗传或光遗传操作，我们观察到，沉默ACC或vHPC神经元的活动减少了在远程时间点的背景恐惧泛化，而刺激ACC或vHPC神经元的活动促进了在最近的时间点的背景恐惧泛化。我们发现，ACC神经元单向投射到vHPC，重要的是，沉默从ACC到vHPC的投射纤维的活动抑制了在远程时间点的背景恐惧泛化。总之，我们的研究结果揭示了ACC到vHPC回路，该回路控制恐惧泛化的表达，并可能提供新的策略来预防或逆转焦虑症受试者，特别是PTSD受试者的背景恐惧泛化。背景恐惧记忆的过度概括是PTSD的一个主要特征，但其背后的电路机制仍不清楚。我们的研究表明，从前扣带皮层到腹侧海马的神经投射控制着情境恐惧泛化的表达。因此，操纵回路可以防止或逆转PTSD受试者的恐惧过度概括。
Contextual fear memory becomes less context-specific over time, a phenomenon referred to as contextual fear generalization. Overgeneralization of contextual fear memory is a core symptom of post-traumatic stress disorder (PTSD), but circuit mechanisms underlying the generalization remain unclear. We show here that neural projections from the anterior cingulate cortex (ACC) to ventral hippocampus (vHPC) mediate contextual fear generalization in male mice. Retrieval of contextual fear in a novel context at a remote time point activated cells in the ACC and vHPC, as indicated by significantly increased C-fos+ cells. Using chemogenetic or photogenetic manipulations, we observed that silencing the activity of ACC or vHPC neurons reduced contextual fear generalization at the remote time point, whereas stimulating the activity of ACC or vHPC neurons facilitated contextual fear generalization at a recent time point. We found that ACC neurons projected to the vHPC unidirectionally, and importantly, silencing the activity of projection fibers from the ACC to vHPC inhibited contextual fear generalization at the remote time point. Together, our findings reveal an ACC to vHPC circuit that controls expression of fear generalization and may offer new strategies to prevent or reverse contextual fear generalization in subjects with anxiety disorders, especially in PTSD. SIGNIFICANCE STATEMENT Overgeneralization of contextual fear memory is a cardinal feature of PTSD, but circuit mechanisms underlying it remain unclear. Our study indicates that neural projections from the anterior cingulate cortex to ventral hippocampus control the expression of contextual fear generalization. Thus, manipulating the circuit may prevent or reverse fear overgeneralization in subjects with PTSD.