Identification of functional circuitry between retrosplenial and postrhinal cortices during fear conditioning.
Identification of functional circuitry between retrosplenial and postrhinal cortices during fear conditioning.
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DOI：
10.1523/jneurosci.2814-12.2012
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发表时间：
2012-08-29
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影响因子：
--
通讯作者：
Bucci DJ
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作者：
Robinson S;Poorman CE;Marder TJ;Bucci DJ
压后皮质 (RSP) 和鼻后皮质 (POR) 与参与学习和记忆的内侧颞叶结构密切相关。先前的研究表明，RSP 和 POR 对于情境恐惧条件反射是必要的，但目前尚不清楚这些区域是单独发挥作用还是作为功能回路共同作用来调节学习和/或记忆。在实验 1 中，使用实时 PCR 和免疫组织化学方法评估了家庭笼养、仅电击、仅情境或恐惧条件大鼠的 RSP 中与学习相关的神经元活动，以量化立即早期基因表达。与所有其他组相比，在恐惧条件大鼠的 RSP 中检测到 Arc（活性调节细胞骨架相关蛋白）mRNA 以及 Arc 和 c-Fos 蛋白表达显着增加。在实验 2 中，逆行追踪结合免疫组织化学显示，与对照组相比，在恐惧条件大鼠中，从 RSP 投射到 POR 的细胞中很大一部分对 c-Fos 呈免疫阳性。这些结果表明，从 RSP 投射到 POR 的神经元在恐惧调节过程中确实很活跃。在实验3中，使用功能性断开范式来进一步检查恐惧条件反射期间RSP和POR之间的相互作用。与对照组相比，大脑对侧RSP和POR单侧损伤的大鼠表现出情境恐惧记忆受损，而与对照组和对侧损伤的大鼠相比，同一半球单侧损伤的大鼠表现出中等水平的冻结。总的来说，这些结果首次表明 RSP 和 POR 作为情境恐惧学习和记忆所必需的皮质网络发挥作用。
The retrosplenial (RSP) and postrhinal (POR) cortices are heavily interconnected with medial temporal lobe structures involved in learning and memory. Previous studies indicate that RSP and POR are necessary for contextual fear conditioning, but it remains unclear whether these regions contribute individually or instead work together as a functional circuit to modulate learning and/or memory. In Experiment 1, learning-related neuronal activity was assessed in RSP from home-cage, shock-only, context-only or fear conditioned rats using real-time PCR and immunohistochemical methods to quantify immediate early gene expression. A significant increase in Arc (activity regulated cytoskeleton-associated protein) mRNA and Arc and c-Fos protein expression was detected in RSP from fear conditioned rats compared to all other groups. In Experiment 2, retrograde tracing combined with immunohistochemistry revealed that compared to controls, a significant proportion of cells projecting from RSP to POR were immunopositive for c-Fos in fear conditioned rats. These results demonstrate that neurons projecting from RSP to POR are indeed active during fear conditioning. In Experiment 3, a functional disconnection paradigm was used to further examine the interaction between RSP and POR during fear conditioning. Compared to controls, rats with unilateral lesions of RSP and POR on opposite sides of the brain exhibited impaired contextual fear memory whereas rats with unilateral lesions in the same hemisphere displayed intermediate levels of freezing compared to controls and rats with contralateral lesions. Collectively these results are the first to show that RSP and POR function as a cortical network necessary for contextual fear learning and memory.