von Engelhardt Jakob, Doganci Beril, Jensen Vidar, Hvalby Øivind, Göngrich Christina, Taylor Amy, Barkus Chris, Sanderson David J, Rawlins J Nicholas P, Seeburg Peter H, Bannerman David M, Monyer Hannah
Department of Clinical Neurobiology, University of Heidelberg, D-69120 Heidelberg, Germany.
Neuron. 2008 Dec 10;60(5):846-60. doi: 10.1016/j.neuron.2008.09.039.
Controversy revolves around the differential contribution of NR2A- and NR2B-containing NMDA receptors, which coexist in principal forebrain neurons, to synaptic plasticity and learning in the adult brain. Here, we report genetically modified mice in which the NR2B subunit is selectively ablated in principal neurons of the entire postnatal forebrain or only the hippocampus. NR2B ablation resulted in smaller NMDA receptor-mediated EPSCs with accelerated decay kinetics, as recorded in CA1 pyramidal cells. CA3-to-CA1 field LTP remained largely unaltered, although a pairing protocol revealed decreased NMDA receptor-mediated charge transfer and reduced cellular LTP. Mice lacking NR2B in the forebrain were impaired on a range of memory tasks, presenting both spatial and nonspatial phenotypes. In contrast, hippocampus-specific NR2B ablation spared hippocampus-dependent, hidden-platform water maze performance but induced a selective, short-term, spatial working memory deficit for recently visited places. Thus, both hippocampal and extra-hippocampal NR2B containing NMDA receptors critically contribute to spatial performance.
争议主要围绕在成年大脑中，共同存在于前脑主要神经元中的含NR2A和含NR2B的NMDA受体对突触可塑性和学习的不同贡献。在此，我们报道了经过基因改造的小鼠，其中NR2B亚基在整个出生后前脑的主要神经元或仅在海马体中被选择性敲除。如在CA1锥体细胞中记录的那样，NR2B敲除导致NMDA受体介导的兴奋性突触后电流（EPSCs）变小，且衰减动力学加快。尽管配对方案显示NMDA受体介导的电荷转移减少且细胞性长时程增强（LTP）降低，但CA3到CA1区的LTP在很大程度上保持不变。在前脑中缺乏NR2B的小鼠在一系列记忆任务中受损，表现出空间和非空间表型。相比之下，海马体特异性NR2B敲除保留了依赖海马体的隐藏平台水迷宫表现，但导致对最近访问地点的选择性短期空间工作记忆缺陷。因此，含有NR2B的海马体和海马体外的NMDA受体对空间表现都至关重要。
