Harvey-Girard Erik, Dunn Robert J, Maler Len
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5.
J Comp Neurol. 2007 Dec 20;505(6):644-68. doi: 10.1002/cne.21521.
Several types of N-methyl-D-aspartate (NMDA) receptor-dependent synaptic plasticity are characterized by differences in polarity, induction parameters, and duration, which depend on the interactions of NMDARs with intracellular synaptic and signaling proteins. Here, we examine the NMDAR signaling components in the brain of the weakly electric fish Apteronotus leptorhynchus. Compared with mammalian orthologs, high levels of sequence conservation for known functional sites in both NMDAR subunits (NR1, NR2A-C) and signaling proteins (fyn tyrosine kinase, RasGRF-1 and -2) were found. In situ hybridization analysis demonstrated that, similar to the case in the adult mammal brain, NR2A and NR2B are expressed at moderate levels in most brain regions and at very high levels in the dorsal telencephalon. RasGRF-1 and fyn have a similar distribution and appear to be coexpressed with NR2B in telencephalic regions known to support learning and long-term memory. Both NR2A and NR2B are highly expressed in pyramidal cells of the electrosensory lateral line lobe (ELL) known to exhibit the short-term synaptic plasticity that underlies adaptive feedback cancellation of redundant sensory input. In contrast, nonplastic pyramidal cells expressed only the NR2A subunit. Furthermore, field recordings show that ifenprodil-sensitive NR2B-containing NMDARs predominate for the plastic feedback input to ELL pyramidal cells. However, RasGRF-1 and fyn are expressed only at low levels in a subset of these pyramidal cells. Our data suggest that NMDAR functions are highly conserved between fish and mammals and that synaptic plasticity dynamics in different brain regions are related to the expression patterns of the synaptic signaling proteins interacting with NMDARs.
几种类型的N-甲基-D-天冬氨酸（NMDA）受体依赖性突触可塑性具有极性、诱导参数和持续时间方面的差异，这些差异取决于NMDAR与细胞内突触和信号蛋白的相互作用。在此，我们研究弱电鱼细吻无背电鳗大脑中的NMDAR信号成分。与哺乳动物的直系同源物相比，在NMDAR亚基（NR1、NR2A - C）和信号蛋白（fyn酪氨酸激酶、RasGRF - 1和 - 2）的已知功能位点发现了高水平的序列保守性。原位杂交分析表明，与成年哺乳动物大脑的情况类似，NR2A和NR2B在大多数脑区中等水平表达，而在背侧端脑高水平表达。RasGRF - 1和fyn具有相似的分布，并且似乎在已知支持学习和长期记忆的端脑区域与NR2B共表达。NR2A和NR2B在电感觉侧线叶（ELL）的锥体细胞中均高度表达，已知这些锥体细胞表现出短期突触可塑性，这是对冗余感觉输入进行适应性反馈消除的基础。相比之下，非可塑性锥体细胞仅表达NR2A亚基。此外，场记录表明，对埃芬地尔敏感的含NR2B的NMDARs在ELL锥体细胞的可塑性反馈输入中占主导地位。然而，RasGRF - 1和fyn仅在这些锥体细胞的一个子集中低水平表达。我们的数据表明，NMDAR功能在鱼类和哺乳动物之间高度保守，并且不同脑区的突触可塑性动态与与NMDAR相互作用的突触信号蛋白的表达模式相关。
