Penke Zsuzsa, Chagneau Carine, Laroche Serge
UMR 8195, Centre de Neurosciences Paris-Sud, Université Paris-Sud Orsay, France.
Front Behav Neurosci. 2011 Aug 17;5:48. doi: 10.3389/fnbeh.2011.00048. eCollection 2011.
Egr1, a member of the Egr family of transcription factors, and Arc are immediate early genes known to play major roles in synaptic plasticity and memory. Despite evidence that Egr family members can control Arc transcriptional regulation, demonstration of a selective role of Egr1 alone is lacking. We investigated the extent to which activity-dependent Arc expression is dependent on Egr1 by analyzing Arc mRNA expression using fluorescence insitu hybridization in the dorsal dentate gyrus and CA1 of wild-type (WT) and Egr1 knockout mice. Following electroconvulsive shock, we found biphasic expression of Arc in area CA1 in mice, consisting in a rapid (30 min) and transient wave followed by a second late-phase of expression (8 h), and a single but prolonged wave of expression in the dentate gyrus. Egr1 deficiency abolished the latest, but not the early wave of Arc expression in CA1, and curtailed that of the dentate gyrus. Since the early wave of Arc expression was not affected in Egr1 mutant mice, we next analyzed behaviorally induced Arc expression patterns as an index of neural ensemble activation in the dentate gyrus and area CA1 of WT and Egr1 mutant mice. Spatial exploration of novel or familiar environments induced in mice a single early and transient wave of Arc expression in the dentate gyrus and area CA1, which were not affected in Egr1 mutant mice. Analyses of Arc-expressing cells revealed that exploration recruits similar size dentate gyrus and CA1 neural ensembles in WT and Egr1 knockout mice. These findings suggest that hippocampal neural ensembles are normally activated immediately following spatial exploration in Egr1 knockout mice, indicating normal hippocampal encoding of information. They also provide evidence that in condition of strong activation Egr1 alone can control late-phases of activity-dependent Arc transcription in the dentate gyrus and area CA1 of the hippocampus.
Egr1是转录因子Egr家族的成员之一，与Arc均为即刻早期基因，已知它们在突触可塑性和记忆中发挥主要作用。尽管有证据表明Egr家族成员可以控制Arc的转录调控，但尚缺乏Egr1单独发挥选择性作用的证据。我们通过使用荧光原位杂交技术分析野生型（WT）和Egr1基因敲除小鼠背侧齿状回及CA1区的Arc mRNA表达，来研究活性依赖的Arc表达在多大程度上依赖于Egr1。电惊厥休克后，我们发现小鼠CA1区Arc呈双相表达，包括一个快速（30分钟）且短暂的波，随后是第二个晚期表达波（8小时），而齿状回中则是单一但持续时间较长的表达波。Egr1基因缺失消除了CA区Arc表达的晚期波，但不影响早期波，并且减少了齿状回中的表达。由于Egr1突变小鼠中Arc表达的早期波未受影响，接下来我们分析行为诱导的Arc表达模式，以此作为WT和Egr1突变小鼠齿状回及CA1区神经群体激活的指标。对新环境或熟悉环境的空间探索在小鼠齿状回和CA1区诱导出单一的早期且短暂的Arc表达波，在Egr1突变小鼠中这些表达波未受影响。对表达Arc的细胞分析显示，WT和Egr1基因敲除小鼠在探索过程中募集的齿状回和CA1神经群体大小相似。这些发现表明，在Egr1基因敲除小鼠中，空间探索后海马神经群体通常会立即被激活，这表明海马对信息的编码正常。它们还提供了证据，表明在强激活条件下，单独的Egr1可以控制海马齿状回和CA1区活性依赖的Arc转录的晚期阶段。
