Egr3, a synaptic activity regulated transcription factor that is essential for learning and memory
Egr3, a synaptic activity regulated transcription factor that is essential for learning and memory
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DOI：
10.1016/j.mcn.2007.02.004
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发表时间：
2007-05-01
影响因子：
3.5
通讯作者：
Tourtellotte, Warren G.
中科院分区：
文献类型：
--
作者：
Li, Lin;Yun, Sung Hwan;Tourtellotte, Warren G.
学习与记忆依赖于在激活神经元中发生的尚不明确的突触和细胞内修饰。丝裂原活化蛋白激酶 - 细胞外调节激酶（MAPK - ERK）信号传导和从头蛋白质合成是持久记忆形成的关键方面，但神经元中MAPK - ERK信号传导的精确效应分子尚未明确界定。早期生长反应（Egr）转录调节因子是受MAPK - ERK调控的基因的实例，并且Egr1（zif268）已被广泛认为对学习和记忆的某些方面至关重要。在此我们表明，与Egr1密切相关的转录调节因子Egr3对正常海马长时程增强（LTP）以及海马和杏仁核依赖性学习与记忆至关重要。在缺乏Egr3的情况下，学习和记忆的缺陷似乎与Egr1无关，因为在杏仁核、海马或皮质中Egr1蛋白水平未改变。此外，与在海马晚期LTP以及某些形式的长期海马和杏仁核依赖性记忆巩固方面存在缺陷的Egr1缺陷型小鼠不同，Egr3缺陷型小鼠在海马早期和晚期LTP以及短期和长期海马和杏仁核依赖性学习与记忆方面存在严重缺陷。因此，Egr3在学习和记忆处理中具有重要作用，这一作用似乎部分不同于Egr1的作用。（C）2007爱思唯尔公司。保留所有权利。
Learning and memory depend upon poorly defined synaptic and intracellular modifications that occur in activated neurons. Mitogen activated protein kinase-extracellular regulated kinase (MAPK-ERK) signaling and de novo protein synthesis are essential aspects of enduring memory formation, but the precise effector molecules of MAPK-ERK signating in neurons are not well defined. Early growth response (Egr) transcriptional regulators are examples of MAPK-ERK regulated genes and Egr1 (zif268) has been widely recognized as essential for some aspects of learning and memory. Here we show that Egr3, a transcriptional regulator closely related to EgrL is essential for normal hippocampal longterm potentiation (LTP) and for hippocampal and amygdala dependent learning and memory. In the absence of Egr3, the defects in learning and memory appear to be independent of Egr1 since Egr1 protein levels are not altered in amygdala, hippocampus or cortex. Moreover, unlike Egr1-deficient mice which have impairments in late phase hippocampal LTP and consolidation of some forms of long-term hippocampus- and amygdala-dependent memory, Egr3-deficient mice have profound defects in early- and late-phase hippocampal LTP, as well as short-term and longterm hippocampus- and amygdala-dependent learning and memory. Thus, Egr3 has an essential role in learning and memory processing that appears to be partly distinct from the role of Egr1 (C) 2007 Elsevier Inc. All rights reserved.