Comprehensive behavioural study of GluR4 knockout mice: implication in cognitive function
Comprehensive behavioural study of GluR4 knockout mice: implication in cognitive function
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DOI：
10.1111/j.1601-183x.2010.00629.x
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发表时间：
2010-11-01
影响因子：
2.5
通讯作者：
Fukumaki, Y.
中科院分区：
文献类型：
--
作者：
Sagata, N.;Iwaki, A.;Fukumaki, Y.
哺乳动物中枢神经系统中的快速兴奋性传递是由AMPA型谷氨酸受体介导的。四聚体AMPA受体复合物由四个亚基GluR 1 -4组成。GluR 4亚基在小脑和出生后早期海马中高度表达，并且被认为通过募集其他AMPA受体亚基参与突触可塑性和功能性神经回路的发育。以前，我们报道了人类GluR 4基因（GRIA 4）与精神分裂症的关联。为了研究GluR 4亚基在高级脑功能中的作用，我们产生了GluR 4敲除小鼠并进行了电生理和行为分析。突变小鼠在海马CA 1区表现出正常的长时程增强（LTP）。GluR 4基因敲除小鼠在T-迷宫测试中表现出轻度改善的空间工作记忆。尽管突变小鼠的空间参考记忆保持完好，但在巴恩斯圆形迷宫测试中空间参考记忆的获得受损。GluR 4基因敲除小鼠表现出受损的前脉冲抑制。这些结果表明GluR 4亚基参与认知功能。
Fast excitatory transmission in the mammalian central nervous system is mediated by AMPA-type glutamate receptors. The tetrameric AMPA receptor complexes are composed of four subunits, GluR1-4. The GluR4 subunit is highly expressed in the cerebellum and the early postnatal hippocampus and is thought to be involved in synaptic plasticity and the development of functional neural circuitry through the recruitment of other AMPA receptor subunits. Previously, we reported an association of the human GluR4 gene (GRIA4) with schizophrenia. To examine the role of the GluR4 subunit in the higher brain function, we generated GluR4 knockout mice and conducted electrophysiological and behavioural analyses. The mutant mice showed normal long-term potentiation (LTP) in the CA1 region of the hippocampus. The GluR4 knockout mice showed mildly improved spatial working memory in the T-maze test. Although the retention of spatial reference memory was intact in the mutant mice, the acquisition of spatial reference memory was impaired in the Barnes circular maze test. The GluR4 knockout mice showed impaired prepulse inhibition. These results suggest the involvement of the GluR4 subunit in cognitive function.