Activity of the anterior cingulate cortex and ventral hippocampus underlie increases in contextual fear generalization
Activity of the anterior cingulate cortex and ventral hippocampus underlie increases in contextual fear generalization
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DOI：
10.1016/j.nlm.2015.07.001
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发表时间：
2015-10-01
影响因子：
2.7
通讯作者：
Jasnow, Aaron M.
中科院分区：
文献类型：
--
作者：
Cullen, Patrick K.;Gilman, T. Lee;Jasnow, Aaron M.
随着时间的推移，对环境的记忆变得不那么具体，导致动物将恐惧从训练环境概括到新环境。尽管人们对情景恐惧记忆长期巩固的神经结构给予了很多关注，但对于随着记忆年龄增长而出现的恐惧泛化增加的机制却知之甚少。在这里，我们研究了C57BL/6J雄性小鼠广义情境恐惧记忆表达的激活神经模式。动物在训练环境或最近和遥远时间点的新环境中接受情境恐惧条件反射和恐惧测试。处死动物，采用荧光原位杂交法检测神经激活情况。我们的研究结果表明，前边缘、边缘下和前扣带（ACC）皮质以及腹侧海马体（vHPC）的活动是泛化恐惧记忆表达的基础。为了验证ACC和vHPC参与泛化恐惧记忆的表达，在检索前，将情境恐惧条件化的动物注入4%利多卡因到ACC、dHPC或vHPC中，以暂时使这些结构失活。结果表明，前扣带皮层和vHPC的活动对于泛化恐惧记忆的表达是必需的，因为这些区域的失活使记忆恢复到上下文精确的形式。当前的背景记忆的时间依赖泛化理论并不能预测vHPC的参与。我们的数据表明该区域在广义记忆中的新作用，应该纳入当前的时间依赖记忆泛化理论。我们还表明，背侧海马体在情境精确记忆中起着长期的作用。我们的研究结果表明，ACC和vHPC之间可能存在相互作用，控制恐惧泛化的表达。(C) 2015爱思唯尔公司版权所有。
Memories for context become less specific with time resulting in animals generalizing fear from training contexts to novel contexts. Though much attention has been given to the neural structures that underlie the long-term consolidation of a context fear memory, very little is known about the mechanisms responsible for the increase in fear generalization that occurs as the memory ages. Here, we examine the neural pattern of activation underlying the expression of a generalized context fear memory in male C57BL/6J mice. Animals were context fear conditioned and tested for fear in either the training context or a novel context at recent and remote time points. Animals were sacrificed and fluorescent in situ hybridization was performed to assay neural activation. Our results demonstrate activity of the prelimbic, infralimbic, and anterior cingulate (ACC) cortices as well as the ventral hippocampus (vHPC) underlie expression of a generalized fear memory. To verify the involvement of the ACC and vHPC in the expression of a generalized fear memory, animals were context fear conditioned and infused with 4% lidocaine into the ACC, dHPC, or vHPC prior to retrieval to temporarily inactivate these structures. The results demonstrate that activity of the ACC and vHPC is required for the expression of a generalized fear memory, as inactivation of these regions returned the memory to a contextually precise form. Current theories of time-dependent generalization of contextual memories do not predict involvement of the vHPC. Our data suggest a novel role of this region in generalized memory, which should be incorporated into current theories of time-dependent memory generalization. We also show that the dorsal hippocampus plays a prolonged role in contextually precise memories. Our findings suggest a possible interaction between the ACC and vHPC controls the expression of fear generalization. (C) 2015 Elsevier Inc. All rights reserved.