Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Japan.
Genes Brain Behav. 2010 Nov;9(8):899-909. doi: 10.1111/j.1601-183X.2010.00629.x.
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.
在哺乳动物中枢神经系统中，快速的兴奋性传递是由 AMPA 型谷氨酸受体介导的。四聚体 AMPA 受体复合物由四个亚基组成，GluR1-4。GluR4 亚基在小脑和出生后早期的海马体中高度表达，被认为通过招募其他 AMPA 受体亚基参与突触可塑性和功能性神经回路的发育。先前，我们报道了人类 GluR4 基因（GRIA4）与精神分裂症有关。为了研究 GluR4 亚基在高级脑功能中的作用，我们生成了 GluR4 敲除小鼠，并进行了电生理和行为分析。突变小鼠在海马 CA1 区表现出正常的长时程增强（LTP）。GluR4 敲除小鼠在 T 迷宫测试中表现出轻微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整，但在 Barnes 圆形迷宫测试中，空间参考记忆的获得受到损害。GluR4 敲除小鼠表现出前脉冲抑制受损。这些结果表明 GluR4 亚基参与认知功能。
