Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1038/s41467-018-02983-w |
Higher ambient synaptic glutamate at inhibitory versus excitatory neurons differentially impacts NMDA receptor activity | |
Yao, Lulu1; Grand, Teddy2; Hanson, Jesse3; Paoletti, Pierre2; Zhou, Qiang1 | |
2018-10-01 | |
发表期刊 | NATURE COMMUNICATIONS
![]() |
ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | Peoples R China; France; USA |
英文摘要 | Selective disruption of synaptic drive to inhibitory neurons could contribute to the pathophysiology of various brain disorders. We have previously identified a GIuN2A-selective positive allosteric modulator, GNE-8324, that selectively enhances N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic responses in inhibitory but not excitatory neurons. Here, we demonstrate that differences in NMDAR subunit composition do not underlie this selective potentiation. Rather, a higher ambient glutamate level in the synaptic cleft of excitatory synapses on inhibitory neurons is a key factor. We show that increasing expression of glutamate transporter 1 (GLT-1) eliminates GNE-8324 potentiation in inhibitory neurons, while decreasing GLT-1 activity enables potentiation in excitatory neurons. Our results reveal an unsuspected difference between excitatory synapses onto different neuronal types, and a more prominent activation of synaptic NMDARs by ambient glutamate in inhibitory than excitatory neurons. This difference has implications for tonic NMDAR activity/signaling and the selective modulation of inhibitory neuron activity to treat brain disorders. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000446113000002 |
WOS关键词 | D-ASPARTATE RECEPTORS ; POSITIVE ALLOSTERIC MODULATION ; AMINO-ACID TRANSPORTERS ; EXTRASYNAPTIC GLUTAMATE ; HIPPOCAMPAL INTERNEURONS ; TIME-COURSE ; EXTRACELLULAR GLUTAMATE ; TONIC ACTIVATION ; PYRAMIDAL CELLS ; RAT-BRAIN |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203677 |
专题 | 资源环境科学 |
作者单位 | 1.Peking Univ, Sch Chem Biol & Biotechnol, Shenzhen Grad Sch, Shenzhen 518055, Peoples R China; 2.Univ PSL, IBENS, Ecole Normale Super, CNRS,INSERM, 46 Rue Ulm, F-75005 Paris, France; 3.Genentech Inc, Dept Neurosci, San Francisco, CA 94080 USA |
推荐引用方式 GB/T 7714 | Yao, Lulu,Grand, Teddy,Hanson, Jesse,et al. Higher ambient synaptic glutamate at inhibitory versus excitatory neurons differentially impacts NMDA receptor activity[J]. NATURE COMMUNICATIONS,2018,9. |
APA | Yao, Lulu,Grand, Teddy,Hanson, Jesse,Paoletti, Pierre,&Zhou, Qiang.(2018).Higher ambient synaptic glutamate at inhibitory versus excitatory neurons differentially impacts NMDA receptor activity.NATURE COMMUNICATIONS,9. |
MLA | Yao, Lulu,et al."Higher ambient synaptic glutamate at inhibitory versus excitatory neurons differentially impacts NMDA receptor activity".NATURE COMMUNICATIONS 9(2018). |
条目包含的文件 | 条目无相关文件。 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论