NMDA GluN2C/2D receptors contribute to synaptic regulation and plasticity in the anterior cingulate cortex of adult mice

Abstract Introduction 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 focuse...

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Main Authors: Qi-Yu Chen, Xu-Hui Li, Jing-Shan Lu, Yinglu Liu, Jung-Hyun Alex Lee, Yu-Xin Chen, Wantong Shi, Kexin Fan, Min Zhuo
Format: Article
Language:English
Published: BMC 2021-03-01
Series:Molecular Brain
Subjects:
Online Access:https://doi.org/10.1186/s13041-021-00744-3
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author Qi-Yu Chen
Xu-Hui Li
Jing-Shan Lu
Yinglu Liu
Jung-Hyun Alex Lee
Yu-Xin Chen
Wantong Shi
Kexin Fan
Min Zhuo
author_facet Qi-Yu Chen
Xu-Hui Li
Jing-Shan Lu
Yinglu Liu
Jung-Hyun Alex Lee
Yu-Xin Chen
Wantong Shi
Kexin Fan
Min Zhuo
author_sort Qi-Yu Chen
collection DOAJ
description Abstract Introduction 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. Results 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. Conclusions 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.
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spelling doaj.art-4f150ea282d74aacbd70d66abde5cd012022-12-21T19:39:56ZengBMCMolecular Brain1756-66062021-03-0114111310.1186/s13041-021-00744-3NMDA GluN2C/2D receptors contribute to synaptic regulation and plasticity in the anterior cingulate cortex of adult miceQi-Yu Chen0Xu-Hui Li1Jing-Shan Lu2Yinglu Liu3Jung-Hyun Alex Lee4Yu-Xin Chen5Wantong Shi6Kexin Fan7Min Zhuo8Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi’an Jiaotong UniversityCenter for Neuron and Disease, Frontier Institutes of Science and Technology, Xi’an Jiaotong UniversityCenter for Neuron and Disease, Frontier Institutes of Science and Technology, Xi’an Jiaotong UniversityCenter for Neuron and Disease, Frontier Institutes of Science and Technology, Xi’an Jiaotong UniversityDepartment of Physiology, University of TorontoCenter for Neuron and Disease, Frontier Institutes of Science and Technology, Xi’an Jiaotong UniversityCenter for Neuron and Disease, Frontier Institutes of Science and Technology, Xi’an Jiaotong UniversityCenter for Neuron and Disease, Frontier Institutes of Science and Technology, Xi’an Jiaotong UniversityCenter for Neuron and Disease, Frontier Institutes of Science and Technology, Xi’an Jiaotong UniversityAbstract Introduction 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. Results 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. Conclusions 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.https://doi.org/10.1186/s13041-021-00744-3NMDARGluN2C/2DACCLTPLTD
spellingShingle Qi-Yu Chen
Xu-Hui Li
Jing-Shan Lu
Yinglu Liu
Jung-Hyun Alex Lee
Yu-Xin Chen
Wantong Shi
Kexin Fan
Min Zhuo
NMDA GluN2C/2D receptors contribute to synaptic regulation and plasticity in the anterior cingulate cortex of adult mice
Molecular Brain
NMDAR
GluN2C/2D
ACC
LTP
LTD
title NMDA GluN2C/2D receptors contribute to synaptic regulation and plasticity in the anterior cingulate cortex of adult mice
title_full NMDA GluN2C/2D receptors contribute to synaptic regulation and plasticity in the anterior cingulate cortex of adult mice
title_fullStr NMDA GluN2C/2D receptors contribute to synaptic regulation and plasticity in the anterior cingulate cortex of adult mice
title_full_unstemmed NMDA GluN2C/2D receptors contribute to synaptic regulation and plasticity in the anterior cingulate cortex of adult mice
title_short NMDA GluN2C/2D receptors contribute to synaptic regulation and plasticity in the anterior cingulate cortex of adult mice
title_sort nmda glun2c 2d receptors contribute to synaptic regulation and plasticity in the anterior cingulate cortex of adult mice
topic NMDAR
GluN2C/2D
ACC
LTP
LTD
url https://doi.org/10.1186/s13041-021-00744-3
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