Institute for Physiology I, Westfälische Wilhelms-Universität Münster, D-48149 Münster, Germany.
Learn Mem. 2012 Apr 17;19(5):194-200. doi: 10.1101/lm.025874.112.
Extinction reduces fear to stimuli that were once associated with an aversive event by no longer coupling the stimulus with the aversive event. Extinction learning is supported by a network comprising the amygdala, hippocampus, and prefrontal cortex. Previous studies implicate a critical role of GABA in extinction learning, specifically the GAD65 isoform of the GABA synthesizing enzyme glutamic acid decarboxylase (GAD). However, a detailed analysis of changes in gene expression of GAD in the subregions comprising the extinction network has not been undertaken. Here, we report changes in gene expression of the GAD65 and GAD67 isoforms of GAD, as measured by relative quantitative real-time RT-PCR, in subregions of the amygdala, hippocampus, and prefrontal cortex 24-26 h after extinction of a recent (1-d) or intermediate (14-d) fear memory. Our results show that extinction of a recent memory induces a down-regulation of Gad65 gene expression in the hippocampus (CA1, dentate gyrus) and an up-regulation of Gad67 gene expression in the infralimbic cortex. Extinguishing an intermediate memory increased Gad65 gene expression in the central amygdala. These results indicate a differential regulation of Gad gene expression after extinction of a recent memory vs. intermediate memory.
extinction 通过不再将刺激与厌恶事件联系起来，从而减少了对曾经与厌恶事件相关的刺激的恐惧。 消退学习由包括杏仁核、海马体和前额叶皮层在内的网络支持。 先前的研究表明 GABA 在消退学习中起着关键作用，特别是 GABA 合成酶谷氨酸脱羧酶（GAD）的 GAD65 同工型。 然而，尚未对构成消退网络的亚区中 GAD 的基因表达变化进行详细分析。 在这里，我们报告了相对定量实时 RT-PCR 测量的在最近（1 天）或中间（14 天）恐惧记忆消退后 24-26 小时，在杏仁核、海马体和前额叶皮层的亚区中 GAD 的 GAD65 和 GAD67 同工型的基因表达变化。 我们的结果表明，近期记忆的消退会导致海马体（CA1、齿状回）中 Gad65 基因表达下调，而边缘下皮层中 Gad67 基因表达上调。 消除中间记忆会增加杏仁核中央区的 Gad65 基因表达。 这些结果表明，最近记忆和中间记忆消退后 Gad 基因表达存在差异调节。
