Department of Experimental Psychology, University of Oxford, South Parks Road, Oxford OX1 3UD, UK.
Biochem Soc Trans. 2009 Dec;37(Pt 6):1323-7. doi: 10.1042/BST0371323.
In recent years, the contribution that different glutamate receptor subtypes and subunits make to spatial learning and memory has been studied extensively using genetically modified mice in which key proteins are knocked out. This has revealed dissociations between different aspects of spatial memory that were not previously apparent from lesion studies. For example, studies with GluA1 AMPAR [AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor] subunit-knockout mice have revealed the presence of a GluA1-dependent, non-associative short-term memory mechanism that is important for performance on spatial working memory tasks, and a GluA1-independent, long-term associative memory mechanism which underlies performance on spatial reference memory tasks. Within this framework we have also studied the contributions of different GluN2-containing NMDARs [NMDA (N-methyl-D-aspartate) receptors] to spatial memory. Studies with GluN2 NMDAR mutants have revealed different contributions from GluN2A- and GluN2B-containing NMDARs to spatial learning. Furthermore, comparison of forebrain- and hippocampus-specific GluN2B-knockout mice has demonstrated that both hippocampal and extra-hippocampal NMDARs make important contributions to spatial memory performance.
近年来，通过使用基因敲除的转基因小鼠对不同谷氨酸受体亚型和亚基在空间学习和记忆中的作用进行了广泛研究。这揭示了以前在损伤研究中不明显的空间记忆的不同方面之间的分离。例如，使用 GluA1 AMPAR [AMPA（α-氨基-3-羟基-5-甲基异恶唑-4-丙酸）受体]亚基敲除小鼠的研究表明，存在一种依赖于 GluA1 的非联想短期记忆机制，对于空间工作记忆任务的表现很重要，以及 GluA1 独立的长期联想记忆机制，它是空间参考记忆任务表现的基础。在这个框架内，我们还研究了不同包含 GluN2 的 NMDA 受体 [NMDA（N-甲基-D-天冬氨酸）受体]对空间记忆的贡献。使用 GluN2 NMDAR 突变体的研究揭示了 GluN2A 和 GluN2B 包含的 NMDAR 对空间学习的不同贡献。此外，比较大脑前部和海马体特异性 GluN2B 敲除小鼠表明，海马体和海马体外的 NMDAR 对空间记忆表现都有重要贡献。
