Neurogranin null mutant mice display performance deficits on spatial learning tasks with anxiety related components

Neurogranin null mutant mice display performance deficits on spatial learning tasks with anxiety related components
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DOI:
10.1002/hipo.1092
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发表时间:
2001-01-01
期刊:
影响因子:
3.5
通讯作者:
Crawley, JN
Crawley, JN
中科院分区:
医学3区
文献类型:
--
作者:
Miyakawa, T;Yared, E;Crawley, JN

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Neurogranin/RC3 是一种与钙调蛋白结合并作为蛋白激酶 C 底物的蛋白质。神经颗粒蛋白分布在海马和前脑的神经元中,在海马锥体细胞的树突棘中高度表达,表明该蛋白与长期增强以及学习和记忆过程有关。神经颗粒蛋白基因 Ng 的无效突变产生了可存活的基因敲除小鼠,用于分析由于神经颗粒蛋白缺失而产生的行为表型。与野生型同窝对照小鼠相比,Ng -/- 小鼠的总体健康状况、神经反射、感觉能力和运动功能均正常。在莫里斯水任务中,Ng -/- 小鼠未能达到隐藏平台测试的获取标准,并且在探测试验中没有表现出选择性搜索。在巴恩斯圆形迷宫(另一项空间导航学习测试)中,Ng -/- 小鼠在某些转移组件上表现出缺陷,但在目标孔周围花费的时间方面表现正常。检测到异常和特殊行为,这似乎代表了 Ng -/- 小鼠的焦虑表型,如在明暗探索测试和开放场中心时间参数中测量的。 Ng -/- 的空间学习明显缺陷和类焦虑倾向的这些发现支持神经颗粒素在海马介导的压力和表现之间的相互作用中的作用。海马 2001;11:763-775。 2001 年 Wiley-Liss, Inc. 出版(匕首)。
Neurogranin/RC3 is a protein that binds calmodulin and serves as a substrate for protein kinase C. Neuronally distributed in the hippocampus and forebrain, neurogranin is highly expressed in dendritic spines of hippocampal pyramidal cells, implicating this protein in longterm potentiation and in learning and memory processes. Null mutation of the neurogranin gene Ng generated viable knockout mice for analysis of the behavioral phenotype resulting from the absence of neurogranin protein. Ng -/- mice were normal on measures of general health, neurological reflexes, sensory abilities, and motor functions, as compared to wild type littermate controls. On the Morris water task, Ng -/- mice failed to reach acquisition criterion on the hidden platform test and did not show selective search on the probe trial. In the Barnes circular maze, another test for spatial navigation learning, Ng -/- mice showed impairments on some components of transfer, but normal performance on time spent around the target hole. Abnormal and idiosyncratic behaviors were detected, that appeared to represent an anxiogenic phenotype in Ng -/- mice, as measured in the lightdark exploration test and the open field center time parameter. These findings of apparent deficits in spatial learning and anxiety-like tendencies in Ng -/- support a role for neurogranin in the hippocampal ly-mediated interaction between stress and performance. Hippocampus 2001;11:763-775. Published 2001 Wiley-Liss, Inc.(dagger).