Enhancing GluN2A-type NMDA receptors impairs long-term synaptic plasticity and learning and memory

	Enhancing GluN2A-type NMDA receptors impairs long-term synaptic plasticity and learning and memory
	Li, QQ; Chen, J; Hu, P; Jia, M; Sun, JH; Feng, HY; Qiao, FC; Zang, YY; Shi, YY; Chen, GQ; Sheng, NY; Xu, Y; Yang, JJ; Xu, ZF; Shi, YS
	2022
发表期刊	MOLECULAR PSYCHIATRY
ISSN	1359-4184
卷号	27 期号:8 页码:3468-3478
摘要	N-methyl-D-aspartic acid type glutamate receptors (NMDARs) play critical roles in synaptic transmission and plasticity, the dysregulation of which leads to cognitive defects. Here, we identified a rare variant in the NMDAR subunit GluN2A (K879R) in a patient with intellectual disability. The K879R mutation enhanced receptor expression on the cell surface by disrupting a KKK motif that we demonstrated to be an endoplasmic reticulum retention signal. Expression of GluN2A_K879R in mouse hippocampal CA1 neurons enhanced the excitatory postsynaptic currents mediated by GluN2A-NMDAR but suppressed those mediated by GluN2B-NMDAR and the AMPA receptor. GluN2A_K879R knock-in mice showed similar defects in synaptic transmission and exhibited impaired learning and memory. Furthermore, both LTP and LTD were severely impaired in the KI mice, likely explaining their learning and memory defects. Therefore, our study reveals a new mechanism by which elevated synaptic GluN2A-NMDAR impairs long-term synaptic plasticity as well as learning and memory.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13545
专题	科研部门_神经突触机制与功能研究组（盛能印）
推荐引用方式 GB/T 7714	Li, QQ,Chen, J,Hu, P,et al. Enhancing GluN2A-type NMDA receptors impairs long-term synaptic plasticity and learning and memory[J]. MOLECULAR PSYCHIATRY,2022,27(8):3468-3478.
APA	Li, QQ.,Chen, J.,Hu, P.,Jia, M.,Sun, JH.,...&Shi, YS.(2022).Enhancing GluN2A-type NMDA receptors impairs long-term synaptic plasticity and learning and memory.MOLECULAR PSYCHIATRY,27(8),3468-3478.
MLA	Li, QQ,et al."Enhancing GluN2A-type NMDA receptors impairs long-term synaptic plasticity and learning and memory".MOLECULAR PSYCHIATRY 27.8(2022):3468-3478.

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