Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, Santa Catarina 88049-900, Brazil.
Learn Mem. 2013 Dec 16;21(1):14-20. doi: 10.1101/lm.032631.113.
The prelimbic cortex has been implicated in the consolidation of previously learned fear. Herein, we report that temporarily inactivating this medial prefrontal cortex subregion with the GABAA agonist muscimol (4.0 nmol in 0.2 μL per hemisphere) was able to equally disrupt 1-, 7-, and 21-d-old contextual fear memories after their brief retrieval in rats. In all cases, this effect was prevented when memory reactivation was omitted. These results indicate that recent and remote fear memories are susceptible to reconsolidation blockade induced by prelimbic cortex inactivation. It was also demonstrated that the disrupting effect of prelimbic cortex inactivation on fear memory persisted over 11 d, and did not show extinction-related features, such as reinstatement. Infusing the same dose and volume of muscimol bilaterally into the infralimbic cortex after brief retrieval/reactivation of the fear memory did not disrupt it, as seen in prelimbic cortex-inactivated animals. The expression of Zif268/Egr1, the product of an immediate early gene related to memory reconsolidation, was also less pronounced in the infralimbic cortex than in prelimbic cortex following memory retrieval/reactivation. Altogether, the present findings highlight that activity in the prelimbic cortex may reestablish reactivated aversive memories and, therefore, contribute to their maintenance over time.
额前皮质在先前习得的恐惧的巩固中起作用。在此，我们报告称，用 GABAA 激动剂 muscimol（每侧脑半球 0.2μL 中 4.0nmol）暂时失活该内侧前额皮质亚区，可在大鼠短暂检索后同样破坏 1 天、7 天和 21 天的情境恐惧记忆。在所有情况下，当省略记忆再激活时，这种效应都会被阻止。这些结果表明，近期和远期的恐惧记忆容易受到额前皮质失活诱导的再巩固阻断。还证明，额前皮质失活对恐惧记忆的破坏作用持续了 11 天，并且没有表现出与消退相关的特征，例如复燃。在短暂检索/再激活恐惧记忆后，将相同剂量和体积的 muscimol 双侧注入下边缘皮质，不会像在额前皮质失活动物中那样破坏恐惧记忆。在记忆检索/再激活后，即刻早期基因产物 Zif268/Egr1 的表达在边缘下皮质也低于额前皮质。总的来说，目前的研究结果强调了额前皮质的活动可能重新建立被重新激活的厌恶记忆，并因此有助于它们随时间的维持。
