Acquisition of conditioned fear is followed by region-specific changes in RNA editing of glutamate receptors
Acquisition of conditioned fear is followed by region-specific changes in RNA editing of glutamate receptors
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DOI：
10.3109/10253890.2015.1073254
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发表时间：
2015-01-01
影响因子：
2.3
通讯作者：
Gaisler-Salomon, Inna
中科院分区：
文献类型：
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作者：
Brande-Eilat, Noa;Golumbic, Yaela N.;Gaisler-Salomon, Inna
腺苷(A)转肌苷(I) RNA编辑是一种影响突触功能的转录后修饰过程。编码kainate GRIK1和AMPA GluA2谷氨酸受体亚基的转录本经过编辑，导致甘氨酸/精氨酸（Q/R）交换和Ca2+通透性降低。我们假设这些地点的编辑可能是经验依赖的、时间动态的和区域特定的。我们在痕量和情境恐惧条件反射方案中训练C57/Bl6小鼠，并在训练后的两个时间点检测杏仁核（CeA）和海马体（CA1和CA3）中GRIK1和GluA2 Q/R位点的编辑水平。我们还研究了RNA编辑酶和编辑靶标表达的经验依赖性变化。在微量恐惧条件反射方案中训练的动物表现出杏仁核中未编辑的GRIK1 RNA的短暂增加，并且它们的学习效率与未编辑的CA1 RNA水平相关。与之前的报道一致，GluA2 RNA编辑水平接近100%。此外，我们观察到杏仁核和海马中RNA编辑酶ADAR2和ADAR1 mRNA表达的经验依赖性变化，以及杏仁核中ADAR2选择性剪接无活性形式的学习依赖性增加。由于未编辑的转录本编码Ca2+渗透性受体亚基，这些发现表明，谷氨酸受体Q/R位点的RNA编辑在经验依赖性突触修饰过程中起重要作用。
Adenosine (A) to inosine (I) RNA editing is a post-transcriptional modification process that can affect synaptic function. Transcripts encoding the kainate GRIK1 and AMPA GluA2 glutamate receptor subunits undergo editing that leads to a glycine/arginine (Q/R) exchange and reduced Ca2+ permeability. We hypothesized that editing at these sites could be experience-dependent, temporally dynamic and region-specific. We trained C57/Bl6 mice in trace and contextual fear conditioning protocols, and examined editing levels at GRIK1 and GluA2 Q/R sites in the amygdala (CeA) and hippocampus (CA1 and CA3), at two time points after training. We also examined experience-dependent changes in the expression of RNA editing enzymes and editing targets. Animals trained in the trace fear conditioning protocol exhibited a transient increase in unedited GRIK1 RNA in the amygdala, and their learning efficiency correlated with unedited RNA levels in CA1. In line with previous reports, GluA2 RNA editing levels were nearly 100%. Additionally, we observed experience-dependent changes in mRNA expression of the RNA editing enzymes ADAR2 and ADAR1 in amygdala and hippocampus, and a learning-dependent increase in the alternatively spliced inactive form of ADAR2 in the amygdala. Since unedited transcripts code for Ca2+-permeable receptor subunits, these findings suggest that RNA editing at Q/R sites of glutamate receptors plays an important role in experience-dependent synaptic modification processes.