Coultrap Steven J, Nixon Kristin M, Alvestad Rachel M, Valenzuela C Fernando, Browning Michael D
Department of Pharmacology, University of Colorado at Denver and Health Sciences Center, Mail Stop 8303, PO Box 6511, Aurora, CO 80045-0511, USA.
Brain Res Mol Brain Res. 2005 Apr 27;135(1-2):104-11. doi: 10.1016/j.molbrainres.2004.12.005.
N-Methyl-d-aspartate (NMDA)-type glutamate receptors in the hippocampus are important mediators of both memory formation and excitotoxicity. It is thought that glutamatergic neurons of the CA1, CA3 and dentate gyrus regions of the hippocampus contribute differentially to memory formation and are differentially sensitive to excitotoxicity. The subunit and/or splice variant composition of the NMDA receptor controls many aspects of receptor function such as ligand affinity, calcium permeability and channel kinetics, as well as interactions with intracellular anchoring and regulatory proteins. Thus, one possible explanation of the differences in NMDA receptor-dependent processes, such as synaptic plasticity and excitotoxicity, among the hippocampal sub-regions is that they differ in subunit and/or splice variant expression. Here we report that the NMDA receptor subunits NR1 and NR2B, along with the four splice variant cassettes of the NR1 subunit are differentially expressed in the CA1, CA3 and dentate gyrus of the hippocampus. Expression of the AMPA receptor subunits GluR1 and GluR2 also differ. These differences may contribute to functional differences, such as with excitotoxicity and synaptic plasticity, that exist between the sub-regions of the hippocampus.
海马体中的N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体是记忆形成和兴奋性毒性的重要介质。据认为，海马体CA1、CA3和齿状回区域的谷氨酸能神经元对记忆形成的贡献不同，对兴奋性毒性的敏感性也不同。NMDA受体的亚基和/或剪接变体组成控制着受体功能的许多方面，如配体亲和力、钙通透性和通道动力学，以及与细胞内锚定和调节蛋白的相互作用。因此，海马体亚区域之间依赖NMDA受体的过程（如突触可塑性和兴奋性毒性）存在差异的一个可能解释是，它们在亚基和/或剪接变体表达上存在差异。我们在此报告，NMDA受体亚基NR1和NR2B，以及NR1亚基的四个剪接变体盒在海马体的CA1、CA3和齿状回中差异表达。AMPA受体亚基GluR1和GluR2的表达也存在差异。这些差异可能导致海马体亚区域之间存在的功能差异，如兴奋性毒性和突触可塑性。
