Behavioral deficits and subregion-specific suppression of LTP in mice expressing a population of mutant NMDA receptors throughout the hippocampus
Behavioral deficits and subregion-specific suppression of LTP in mice expressing a population of mutant NMDA receptors throughout the hippocampus
复制标题
DOI：
10.1101/lm.1316909
复制
发表时间：
2009-10-01
影响因子：
2
通讯作者：
Schoepfer, Ralf
中科院分区：
文献类型：
--
作者：
Chen, Philip E.;Errington, Michael L.;Schoepfer, Ralf
NMDA受体（NMDAR）亚基GluN 1是NMDAR的一个强制性组成部分，没有已知的功能同源物，并在几乎所有神经元细胞类型中表达。NMDAR系统是一个重合检测器，在空间学习和突触可塑性中起着关键作用。其符合检测特性对于海马长时程增强（LTP）的诱导至关重要。我们已经产生了一个突变小鼠模型表达的Grin 1（N598 R）等位基因的亚型，这导致少数（约10%）的重合检测受损的NMDAR。令人惊讶的是，这些动物在海马结构的齿状回（DG）中发现了特定的功能变化。早期LTP在体内CA 1区正常表达，但在DG的穿通通路-颗粒细胞突触中被完全抑制。此外，在DG中诱发的群体尖峰的幅度有明显的减少。这些特定的变化伴随着空间识别，空间学习，逆转学习和保持的行为障碍。我们的数据表明，GluN 1依赖的NMDAR生理学的微小变化，可以引起显着的后果，在突触信号在一个分区特定的方式，尽管非冗余性质的GluN 1基因及其全球表达。
The NMDA receptor (NMDAR) subunit GluN1 is an obligatory component of NMDARs without a known functional homolog and is expressed in almost every neuronal cell type. The NMDAR system is a coincidence detector with critical roles in spatial learning and synaptic plasticity. Its coincidence detection property is crucial for the induction of hippocampal long-term potentiation (LTP). We have generated a mutant mouse model expressing a hypomorph of the Grin1(N598R) allele, which leads to a minority (about 10%) of coincidence detection-impaired NMDARs. Surprisingly, these animals revealed specific functional changes in the dentate gyrus (DG) of the hippocampal formation. Early LTP was expressed normally in area CA1 in vivo, but was completely suppressed at perforant path-granule cell synapses in the DG. In addition, there was a pronounced reduction in the amplitude of the evoked population spike in the DG. These specific changes were accompanied by behavioral impairments in spatial recognition, spatial learning, reversal learning, and retention. Our data show that minor changes in GluN1-dependent NMDAR physiology can cause dramatic consequences in synaptic signaling in a subregion-specific fashion despite the nonredundant nature of the GluN1 gene and its global expression.