摘要
大脑皮层中兴奋和抑制系统之间的动态平衡决定了皮层神经元对刺激的反应特性.已有研究表明,二甲双胍能够诱导γ-氨基丁酸受体向突触后膜聚集,增强神经系统的抑制效果.本课题进一步探讨了二甲双胍对初级视觉皮层兴奋和抑制系统平衡的调节作用,以及其改善小鼠视觉功能的潜力.实验使用成年雄性小鼠,实验组(metformin)10只每天给予二甲双胍250 mg/kg,对照组(control)6只每天给予0.3 ml生理盐水,灌胃处理3周.结果发现二甲双胍可以显著升高囊泡GABA转运蛋白VGAT和突触后抑制性递质受体相关蛋白Gephyrin的合成.此外,它显著降低突触后兴奋性受体Glu A1和Glu N1的表达.多通道电极电生理记录结果显示,二甲双胍作用下小鼠初级视觉皮层的自发放和诱发放显著降低,而信噪比、方向和方位选择性显著增加.实验结果表明,二甲双胍可以通过降低兴奋突触、增强抑制突触,调节初级视皮层的兴奋——抑制平衡,提高信息处理能力,增强视觉功能.
The dynamic balance of excitation and inhibition systems in the cerebral cortex determine the response characteristics of neurons to the stimulation.It has been reported that metformin can induce the postsynaptic clustering of gamma-aminobutyric acid(GABA)receptors and enhance inhibition in the nervous system.Here we explore the regulatory effect of metformin on the balance of the excitatory and the inhibitory system of the primary visual cortex,and its potential to improve visual function in mice.Adult male mice were treated with metformin(metformin group)and normal saline(control group)for 3 weeks of intragastril administration.We found that metformin can significantly increase the production of vesicle GABA transporter(VGAT)and postsynaptic inhibitory receptor-related protein(Gephyrin).Furthermore,it significantly reduced the expression of postsynaptic excitatory receptors Glu A1 and Glu N1.The data also demonstrated that the multichannel electrode recording shows that Baseline Response and Maximum Response of the primary visual cortex were significantly decreased,while under the treatment of metformin the signal-to-noise ratio,directional and orientation bias were significantly increased.Our finding reveals that metformin could reduce the excitation synapse,enhance the inhibition synapse,and adjust the balance of excitation-inhibition of the primary visual cortex,thus improving information processing ability and enhancing visual function.
作者
蔡阳
李保炜
周逸峰
CAI Yang;LI Bao-Wei;ZHOU Yi-Feng(School of Life Sciences,University of Science and Technology of China,Hefei 230027,China)
出处
《生物化学与生物物理进展》
SCIE
CAS
CSCD
北大核心
2021年第4期465-474,共10页
Progress In Biochemistry and Biophysics
基金
国家自然科学基金(31571074,91749102)资助项目.
关键词
二甲双胍
初级视觉皮层
多通道电极
兴奋系统
抑制系统
metformin
primary visual cortex
multi-channel electrode
excitation system
inhibition system
