Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
International Institute for Brain Research, Qingdao International Academician Park, Qingdao, China.
Mol Brain. 2021 Mar 25;14(1):60. doi: 10.1186/s13041-021-00744-3.
N-Methyl-D-aspartate receptors (NMDARs) play a critical role in different forms of plasticity in the central nervous system. NMDARs are always assembled in tetrameric form, in which two GluN1 subunits and two GluN2 and/or GluN3 subunits combine together. Previous studies focused mainly on the hippocampus. The anterior cingulate cortex (ACC) is a key cortical region for sensory and emotional functions. NMDAR GluN2A and GluN2B subunits have been previously investigated, however much less is known about the GluN2C/2D subunits.
In the present study, we found that the GluN2C/2D subunits are expressed in the pyramidal cells of ACC of adult mice. Application of a selective antagonist of GluN2C/2D, (2R*,3S*)-1-(9-bromophenanthrene-3-carbonyl) piperazine-2,3-dicarboxylic acid (UBP145), significantly reduced NMDAR-mediated currents, while synaptically evoked EPSCs were not affected. UBP145 affected neither the postsynaptic long-term potentiation (post-LTP) nor the presynaptic LTP (pre-LTP). Furthermore, the long-term depression (LTD) was also not affected by UBP145. Finally, both UBP145 decreased the frequency of the miniature EPSCs (mEPSCs) while the amplitude remained intact, suggesting that the GluN2C/2D may be involved in presynaptic regulation of spontaneous glutamate release.
Our results provide direct evidence that the GluN2C/2D contributes to evoked NMDAR mediated currents and mEPSCs in the ACC, which may have significant physiological implications.
N-甲基-D-天冬氨酸受体（NMDARs）在中枢神经系统的不同形式的可塑性中起着关键作用。NMDARs 总是以四聚体的形式组装，其中两个 GluN1 亚基和两个 GluN2 和/或 GluN3 亚基结合在一起。以前的研究主要集中在海马体上。前扣带皮层（ACC）是感觉和情绪功能的关键皮质区域。以前已经研究了 NMDAR GluN2A 和 GluN2B 亚基，但对 GluN2C/2D 亚基的了解要少得多。
在本研究中，我们发现 GluN2C/2D 亚基在成年小鼠 ACC 的锥体神经元中表达。应用 NMDAR GluN2C/2D 的选择性拮抗剂（2R*，3S*）-1-（9-溴菲-3-羰基）哌嗪-2,3-二羧酸（UBP145），可显著减少 NMDAR 介导的电流，而突触诱发的 EPSC 不受影响。UBP145 既不影响突触后长时程增强（post-LTP），也不影响突触前长时程增强（pre-LTP）。此外，长时程抑制（LTD）也不受 UBP145 影响。最后，UBP145 均降低了微小兴奋性突触后电流（mEPSCs）的频率，而幅度保持不变，表明 GluN2C/2D 可能参与了突触前自发谷氨酸释放的调节。
我们的研究结果直接证明了 GluN2C/2D 有助于 ACC 中诱发的 NMDAR 介导的电流和 mEPSCs，这可能具有重要的生理意义。
