ISSN 0371-0874, CN 31-1352/Q

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α7-nAChR基因敲除小鼠海马神经元突触传递和神经网络的电生理表型

郑 超*,高凌云,张环环,查盈盈,汪萌芽*

皖南医学院细胞电生理研究室,芜湖 241002

摘要

研究显示,含有α7亚基的烟碱型乙酰胆碱受体(α7-nicotinic acetylcholine receptor, α7-nAChR)基因敲除(α7 KO)的小鼠表现出很少的功能表型,本文旨在研究α7 KO对小鼠海马电生理特征的影响。用标准胞外场电位记录评估α7 KO对小鼠海马CA3-CA1突触传递的影响,用穿孔膜片钳记录检测小鼠海马单个的神经元γ-氨基丁酸A型受体(γ-aminobutyric acid A-type receptor, GABAA-R)的电生理学表型。结果显示,与野生型小鼠相比,α7 KO小鼠海马CA1神经元场兴奋性突触后电位(field excitatory postsynaptic potential, fEPSP)斜率显著降低,卡巴胆碱诱发的θ振荡显著减少。在给予GABAA-R激动剂蝇覃醇(muscimol)条件下,与野生型小鼠相比,α7 KO小鼠海马CA1和CA3神经元I–V曲线均向去极化方向明显移动。以上结果提示,α7 KO小鼠海马CA3-CA1突触传递显著受损,GABAA-R成熟显著延迟,表明α7-nAChR基因缺失可显著改变海马的电生理功能,这可能为α7-nAChR在海马功能和海马相关疾病中作用的理解提供了新的认识。

关键字: 海马;烟碱型乙酰胆碱受体;基因敲除;发育;突触传递;神经振荡;

分类号:R338.8

Electrophysiological phenotypes of synaptic transmission and neural network in hippocampal neurons of the mice null α7-nAChRs

ZHENG Chao*, GAO Ling-Yun, ZHANG Huan-Huan, ZHA Ying-Ying, WANG Meng-Ya*

Cell Electrophysiology Laboratory, Wannan Medical College, Wuhu, 241002, China

Abstract

It was reported that α7 subunit of nicotinic acetylcholine receptor (α7-nAChR) knockout (α7 KO) mice showed few functional phenotypes. The purpose of this study was to study the effect of α7 KO on the electrophysiological characteristics of hippocampus in mice. The effect of α7 KO on hippocampal CA3-CA1 synaptic transmission in mice was evaluated by standard extracellular field potential recordings. The electrophysiological phenotype of γ-aminobutyrate A receptors (GABAA-Rs) of single hippocampal neuron was detected by perforated patch-clamp recordings. The results showed that, the slope of field excitatory postsynaptic potential (fEPSP) and carbachol-induced θ oscillation were significantly decreased in the hippocampal CA1 neurons of α7 KO mice, compared with those of wild type mice. Under the treatment of GABAA-R agonist muscimol, the I–V curves of both the hippocampal CA1 and CA3 neurons of α7 KO mice shifted towards depolarizing direction obviously, compared with those of wild type mice. These results suggest that the hippocampal CA3-CA1 synaptic transmission in α7 KO mice was significantly impaired and GABAA-R maturation was significantly delayed, suggesting that the deletion of α7-nAChR gene could significantly change the electrophysiological function of the hippocampus. The results may provide a new understanding of the role of α7-nAChR in hippocampal function and associated diseases.

Key words: hippocampus; nicotinic acetylcholine receptor (nAChR); gene knockout; development; synaptic transmission; neural oscillations;

收稿日期:2018-04-26  录用日期:2018-10-24

  

DOI: 10.13294/j.aps.2018.0089