• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

成年期新皮质网络中GABA受体信号传导的系统发育分歧。

Phylogenetic divergence of GABA receptor signaling in neocortical networks over adult life.

作者信息

Wilson Max A, Sumera Anna, Taylor Lewis W, Meftah Soraya, McGeachan Robert I, Modebadze Tamara, Jayasekera B Ashan P, Cowie Christopher J A, LeBeau Fiona E N, Liaquat Imran, Durrant Claire S, Brennan Paul M, Booker Sam A

机构信息

Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, EH8 9XD, UK.

Simons Initiative for the Developing Brain, University of Edinburgh, Edinburgh, EH8 9XD, UK.

出版信息

Nat Commun. 2025 May 6;16(1):4194. doi: 10.1038/s41467-025-59262-8.

DOI:10.1038/s41467-025-59262-8
PMID:40328769
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12056048/
Abstract

Cortical circuit activity is controlled by GABA-mediated inhibition in a spatiotemporally restricted manner. GABA receptor (GABAR) signalling exerts powerful slow inhibition that controls synaptic, dendritic and neuronal activity. But, how GABARs contribute to circuit-level inhibition over the lifespan of rodents and humans is poorly understood. In this study, we quantitatively determined the functional contribution of GABAR signalling to pre- and postsynaptic domains in rat and human cortical principal cells. We find that postsynaptic GABAR differentially control pyramidal cell activity within the cortical column as a function of age in rodents, but minimally change over adult life in humans. Presynaptic GABARs exert stronger inhibition in humans than rodents. Pre- and postsynaptic GABARs contribute to co-ordination of local information processing in a layer- and species-dependent manner. Finally, we show that GABAR signalling is elevated in patients that have received the anti-seizure medication Levetiracetam. These data directly increase our knowledge of translationally relevant local circuit dynamics, with direct impact on understanding the role of GABARs in the treatment of seizure disorders.

摘要

皮质回路活动由GABA介导的抑制以时空受限的方式控制。GABA受体（GABAR）信号传导发挥强大的慢抑制作用，控制突触、树突和神经元活动。但是，GABAR如何在啮齿动物和人类的整个生命周期中对回路水平的抑制起作用，目前还知之甚少。在这项研究中，我们定量确定了GABAR信号传导对大鼠和人类皮质主细胞突触前和突触后区域的功能贡献。我们发现，在啮齿动物中，突触后GABAR根据年龄差异控制皮质柱内锥体细胞的活动，但在人类成年期变化极小。突触前GABAR在人类中比在啮齿动物中发挥更强的抑制作用。突触前和突触后GABAR以层和物种依赖的方式促进局部信息处理的协调。最后，我们表明，接受抗癫痫药物左乙拉西坦治疗的患者中GABAR信号传导增强。这些数据直接增加了我们对与转化相关的局部回路动力学的了解，对理解GABAR在癫痫疾病治疗中的作用有直接影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e3f/12056048/45603187f739/41467_2025_59262_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e3f/12056048/5ba5d788f059/41467_2025_59262_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e3f/12056048/4182828f1b3b/41467_2025_59262_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e3f/12056048/b56c17689586/41467_2025_59262_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e3f/12056048/44ad4b1fafb7/41467_2025_59262_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e3f/12056048/abb23994dc52/41467_2025_59262_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e3f/12056048/4d5dcbdbb47a/41467_2025_59262_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e3f/12056048/728ad4f24aeb/41467_2025_59262_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e3f/12056048/45603187f739/41467_2025_59262_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e3f/12056048/5ba5d788f059/41467_2025_59262_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e3f/12056048/4182828f1b3b/41467_2025_59262_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e3f/12056048/b56c17689586/41467_2025_59262_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e3f/12056048/44ad4b1fafb7/41467_2025_59262_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e3f/12056048/abb23994dc52/41467_2025_59262_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e3f/12056048/4d5dcbdbb47a/41467_2025_59262_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e3f/12056048/728ad4f24aeb/41467_2025_59262_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e3f/12056048/45603187f739/41467_2025_59262_Fig8_HTML.jpg

相似文献

1
Phylogenetic divergence of GABA receptor signaling in neocortical networks over adult life.成年期新皮质网络中GABA受体信号传导的系统发育分歧。
Nat Commun. 2025 May 6;16(1):4194. doi: 10.1038/s41467-025-59262-8.
2
Inhibition of BK channels by GABAb receptors enhances intrinsic excitability of layer 2/3 vasoactive intestinal polypeptide-expressing interneurons in mouse neocortex.GABAb受体对大电导钙激活钾通道的抑制增强了小鼠新皮质中表达血管活性肠肽的第2/3层中间神经元的内在兴奋性。
J Physiol. 2025 Mar;603(5):1171-1196. doi: 10.1113/JP286439. Epub 2025 Feb 3.
3
GABA receptors in neocortical and hippocampal pyramidal neurons are coupled to different potassium channels.在新皮层和海马锥体神经元中的 GABA 受体与不同的钾通道偶联。
Eur J Neurosci. 2017 Dec;46(12):2859-2866. doi: 10.1111/ejn.13777. Epub 2017 Dec 8.
4
Loss of constitutive functional γ-aminobutyric acid type A-B receptor crosstalk in layer 5 pyramidal neurons of human epileptic temporal cortex.人类癫痫颞叶皮质第 5 层锥体神经元中组成型功能性 γ-氨基丁酸 A 型-B 型受体串扰的丧失。
Epilepsia. 2018 Feb;59(2):449-459. doi: 10.1111/epi.13991. Epub 2017 Dec 28.
5
Deficits in the activity of presynaptic γ-aminobutyric acid type B receptors contribute to altered neuronal excitability in fragile X syndrome.突触前B型γ-氨基丁酸受体活性的缺陷导致脆性X综合征中神经元兴奋性的改变。
J Biol Chem. 2017 Apr 21;292(16):6621-6632. doi: 10.1074/jbc.M116.772541. Epub 2017 Feb 17.
6
Direct Interaction of PP2A Phosphatase with GABA Receptors Alters Functional Signaling.蛋白磷酸酶 2A 直接与 GABA 受体相互作用改变功能性信号转导。
J Neurosci. 2020 Apr 1;40(14):2808-2816. doi: 10.1523/JNEUROSCI.2654-19.2020. Epub 2020 Feb 28.
7
Somatostatin-expressing interneurons modulate neocortical network through GABAb receptors in a synapse-specific manner.生长抑素表达中间神经元通过 GABA 受体以突触特异性方式调节新皮层网络。
Sci Rep. 2023 May 31;13(1):8780. doi: 10.1038/s41598-023-35890-2.
8
Postsynaptic GABA-receptor mediated currents in diverse dentate gyrus interneuron types.不同齿状回中间神经元类型的突触后 GABA 受体介导的电流。
Hippocampus. 2024 Oct;34(10):551-562. doi: 10.1002/hipo.23628. Epub 2024 Aug 13.
9
Non-hyperpolarizing GABAB receptor activation regulates neuronal migration and neurite growth and specification by cAMP/LKB1.非超极化 GABAB 受体激活通过 cAMP/LKB1 调节神经元迁移和突起生长及定向。
Nat Commun. 2013;4:1800. doi: 10.1038/ncomms2820.
10
Differential surface density and modulatory effects of presynaptic GABA receptors in hippocampal cholecystokinin and parvalbumin basket cells.海马胆囊收缩素和小白蛋白篮状细胞中突触前 GABA 受体的差异表面密度和调节作用。
Brain Struct Funct. 2017 Nov;222(8):3677-3690. doi: 10.1007/s00429-017-1427-x. Epub 2017 May 2.

本文引用的文献

1
Divergent actions of physiological and pathological amyloid-β on synapses in live human brain slice cultures.生理和病理β-淀粉样蛋白对活人脑切片培养物中突触的不同作用。
Nat Commun. 2025 Apr 30;16(1):3753. doi: 10.1038/s41467-025-58879-z.
2
Established and emerging GABA receptor pharmacotherapy for epilepsy.用于癫痫的已确立和新兴的γ-氨基丁酸（GABA）受体药物治疗
Front Pharmacol. 2024 Feb 21;15:1341472. doi: 10.3389/fphar.2024.1341472. eCollection 2024.
3
p-tau Ser356 is associated with Alzheimer's disease pathology and is lowered in brain slice cultures using the NUAK inhibitor WZ4003.
p-tau Ser356 与阿尔茨海默病病理有关，使用 NUAK 抑制剂 WZ4003 可降低脑切片培养物中的 p-tau Ser356 水平。
Acta Neuropathol. 2024 Jan 4;147(1):7. doi: 10.1007/s00401-023-02667-w.
4
Somatostatin-expressing interneurons modulate neocortical network through GABAb receptors in a synapse-specific manner.生长抑素表达中间神经元通过 GABA 受体以突触特异性方式调节新皮层网络。
Sci Rep. 2023 May 31;13(1):8780. doi: 10.1038/s41598-023-35890-2.
5
Current Best Practices for Analysis of Dendritic Spine Morphology and Number in Neurodevelopmental Disorder Research.神经发育障碍研究中树突棘形态和数量分析的当前最佳实践。
ACS Chem Neurosci. 2023 May 3;14(9):1561-1572. doi: 10.1021/acschemneuro.3c00062. Epub 2023 Apr 18.
6
Local connectivity and synaptic dynamics in mouse and human neocortex.小鼠和人类大脑新皮层的局部连接和突触动力学。
Science. 2022 Mar 11;375(6585):eabj5861. doi: 10.1126/science.abj5861.
7
Tonic GABA Receptor-Mediated Currents of Human Cortical GABAergic Interneurons Vary Amongst Cell Types.人类皮质 GABA 能中间神经元的紧张型 GABA 受体介导的电流在细胞类型之间存在差异。
J Neurosci. 2021 Nov 24;41(47):9702-9719. doi: 10.1523/JNEUROSCI.0175-21.2021. Epub 2021 Oct 19.
8
Human neocortical expansion involves glutamatergic neuron diversification.人类新皮层扩张涉及谷氨酸能神经元的多样化。
Nature. 2021 Oct;598(7879):151-158. doi: 10.1038/s41586-021-03813-8. Epub 2021 Oct 6.
9
Comparative cellular analysis of motor cortex in human, marmoset and mouse.人类、狨猴和小鼠运动皮层的比较细胞分析。
Nature. 2021 Oct;598(7879):111-119. doi: 10.1038/s41586-021-03465-8. Epub 2021 Oct 6.
10
GABA Receptor-Mediated Regulation of Dendro-Somatic Synergy in Layer 5 Pyramidal Neurons.γ-氨基丁酸受体介导的对第5层锥体神经元树突-胞体协同作用的调节
Front Cell Neurosci. 2021 Aug 25;15:718413. doi: 10.3389/fncel.2021.718413. eCollection 2021.