An endogenous inhibitor of calcium/calmodulin-dependent kinase II is up-regulated during consolidation of fear memory
An endogenous inhibitor of calcium/calmodulin-dependent kinase II is up-regulated during consolidation of fear memory
复制标题
DOI：
10.1111/j.1460-9568.2006.04830.x
复制
发表时间：
2006-06-01
影响因子：
3.4
通讯作者：
Giese, K. Peter
中科院分区：
文献类型：
--
作者：
Lepicard, Eve M.;Mizuno, Keiko;Giese, K. Peter
CaMKIINα和CaMKIINβ是丰富的突触蛋白--钙/钙调蛋白依赖性蛋白激酶II(CaMKII)的内源性抑制物。CaMKII在记忆形成中起重要作用，内源性抑制物可能是这一过程中CaMKII活性的重要调节因子。在这里，我们调查了在背景背景恐惧条件作用后，CaMKIINα和CaMKIINβ基因在小鼠海马区和杏仁核中的表达是否受到调控。实时荧光定量聚合酶链式反应显示，缺血30分钟和60分钟后，大鼠海马区CaMKIINαmRNA表达上调。相反，CaMKIINβmRNA的表达没有变化。CaMKIINα表达的上调对于恐惧记忆是特异的，因为单独的背景和休克对照不会引起转录水平的任何变化。原位杂交信号定量显示，训练30min后，CaMKIINα在海马区CA1区、齿状回(DG)和杏仁外侧核(LA)的表达增加。我们的发现表明，在巩固恐惧记忆的过程中，内源性抑制基因CaMKIINα的表达上调。上调基因的早起效和上调幅度与即刻早基因相似。综上所述，我们的结果表明，CaMKIINα抑制剂在记忆巩固的早期阶段就具有控制CaMKII活性的生理作用。
CaMKIIN alpha and CaMKIIN beta are endogenous inhibitors of the abundant synaptic protein, calcium/calmodulin-dependent protein kinase II (CaMKII). CaMKII exerts a prominent function in memory formation and the endogenous inhibitors might be important regulators of CaMKII activity during this process. Here we investigated whether or not CaMKIIN alpha and CaMKIIN beta gene expressions are regulated in the mouse hippocampus and amygdala after background contextual fear conditioning. Quantitative real-time PCR revealed that the hippocampal expression of CaMKIIN alpha mRNA was up-regulated 30 and 60 min after conditioning. In contrast, CaMKIIN beta mRNA expression did not change. The up-regulation of CaMKIIN alpha expression was specific for the fear memory because the context alone and a shock control did not induce any variation of transcription level. Quantification of in situ hybridization signals showed that CaMKIIN alpha expression increased in hippocampal area CA1, in the dentate gyrus (DG) and in the lateral amygdala (LA) 30 min after training. Our findings show an up-regulation in the expression of the endogenous inhibitor gene CaMKIIN alpha during consolidation of fear memory. The early onset and the amplitude of the up-regulation are similar to those of immediate-early genes. Taken together, our results suggest that the CaMKIIN alpha inhibitor has a physiological role in controlling CaMKII activity from an early stage of memory consolidation.