Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network
Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network
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DOI：
10.1126/science.1140263
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发表时间：
2007-07-06
期刊：
影响因子：
56.9
通讯作者：
Tonegawa, Susumu
中科院分区：
文献类型：
--
作者：
McHugh, Thomas J.;Jones, Matthew W.;Tonegawa, Susumu
形成多种背景、地点和情节的不同表征是海马体的一项重要功能。齿状回亚区被认为可以发挥这一作用。我们通过产生和分析一种缺乏N-甲基-D-天冬氨酸(NMDA)受体NR1基本亚单位编码基因的小鼠品系来检验这一假设，特别是在齿状回颗粒细胞中。突变小鼠在情景恐惧条件反射中表现正常，但区分两个相似情景的能力受到了损害。当突变小鼠从一种环境转移到另一种环境时，在CA3锥体细胞中观察到特定于环境的放电频率调制显著降低。这些结果表明，齿状回颗粒细胞中的NMDA受体在模式分离过程中起着重要作用。
Forming distinct representations of multiple contexts, places, and episodes is a crucial function of the hippocampus. The dentate gyrus subregion has been suggested to fulfill this role. We have tested this hypothesis by generating and analyzing a mouse strain that lacks the gene encoding the essential subunit of the N-methyl-D-aspartate (NMDA) receptor NR1, specifically in dentate gyrus granule cells. The mutant mice performed normally in contextual fear conditioning, but were impaired in the ability to distinguish two similar contexts. A significant reduction in the context-specific modulation of firing rate was observed in the CA3 pyramidal cells when the mutant mice were transferred from one context to another. These results provide evidence that NMDA receptors in the granule cells of the dentate gyrus play a crucial role in the process of pattern separation.