Mice lacking the ERK1 isoform of MAP kinase are unimpaired in emotional learning

Mice lacking the ERK1 isoform of MAP kinase are unimpaired in emotional learning
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DOI:
10.1101/lm.37001
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发表时间:
2001-01-01
期刊:
影响因子:
2
通讯作者:
Sweatt, JD
Sweatt, JD
中科院分区:
医学4区
文献类型:
--
作者:
Selcher, JC;Nekrasova, T;Sweatt, JD

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细胞外信号调节激酶(ERK)是丝裂原活化蛋白激酶(MAPK)超家族的成员,并且最近在学习和记忆领域获得了相当大的关注。ERK激活已被证明是诱导大鼠海马中的长时程增强(LTP)以及大鼠和小鼠中的联想记忆和空间记忆的形成所必需的。然而,ERK的两种亚型的各自作用尚未被破译。为了研究MAPK的ERK 1(p44)亚型对哺乳动物学习的具体贡献,我们对缺乏ERK 1基因的小鼠进行了一般的行为和生理表征。ERK 1-null动物在旷场试验中表现出显著更高的活性水平。然而,在我们的行为测试中,我们在ERK 1敲除小鼠中没有观察到其他明显的缺陷。具体而言,没有观察到差异的收购或保留(训练后24小时和2周)的背景或线索恐惧条件之间的ERK 1(-/-)和野生型同窝对照。此外,在被动回避试验中未观察到学习表型。当分析海马切片时,我们发现海马CA 1区的基线突触传递或破伤风诱导的LTP没有缺陷。我们发现ERK 2(p42 MAPK)的表达没有明显的代偿性变化。我们的结论是,海马和杏仁核依赖的情绪学习并不严重依赖于ERK 1的活性。
The extracellular signal-regulated kinases (ERKs) are members of the mitogen-activated protein kinase (MAPK) superfamily of enzymes and have recently garnered considerable attention in the field of learning and memory. ERK activation has been shown to be required for the induction of long-term potentiation (LTP) in the rat hippocampus and for the formation of associative and spatial memories in both the rat and the mouse. However, the individual roles for the two isoforms of ERK have yet to be deciphered. To investigate the specific contribution of the ERK1 (p44) isoform of MAPK to mammalian learning, we performed a general behavioral and physiological characterization of mice lacking the ERK1 gene. The ERK1-null animals demonstrated significantly higher levels of activity in the open field test. However, we observed no other discernible deficits in the ERK1 knockout mice in our behavioral testing. Specifically, no differences were observed in the acquisition or retention (24 h and 2 wk after training) of either contextual or cue fear conditioning between the ERK1(-/-) and their wild-type littermate controls. In addition, no learning phenotype was observed in the passive avoidance test. When hippocampal slices were analyzed, we found no deficits in baseline synaptic transmission or in tetanus-induced LTP in hippocampal area CA1. We found no apparent compensatory changes in the expression of ERK2 (p42 MAPK). We conclude that hippocampus and amygdala-dependent emotional learning does not depend critically on the activity of ERK1.