GABA能去抑制水平的变化对海马CAl突触长时程增强的影响

摘要

Objective To investigate the effects of GABAergic inhibition medicated by the intemeurons on the induction of long-term potentiation (LPT), and determine the concentration of bicuculline required to block GABAA receptor-mediated inhibition and affect LIT induction at CA1 hippocampal synapse. Methods Using whole-cell recording technique, the mini-inhibitory postsynaptic current (mIPSC) and evoked fcedforward inhibitory post synaptic current (IPSC) were measured from the CA1 neurons in the hippocampal slices. Extracellular recording of field excitatory postsynaptic potential (fEPSP) by Schaffer collateral stimulation was used to study the synaptic plasticity in adult mice hippocampal slices, and the effects of bicuculline at different concentrations on mlPSC, IPSC, fEPSP and LTP induction were evaluated. Results Bicuuclline at 10 and 20 μmol/L abolished mIPSC and IPSC currents. The action of 20 μmol/L bicuuclline were more obviously. The slope of fEPSPs were significantly enhanced by application of bicuculline at 20 μmol/L, but not at 5 or 10 μmol/L. In the presence of 5, 10, 20 and 50 μmol/L bicuculline, LTP of the fEPSP slope following 100 Hz tetanization was enhanced, but the increment was significant only for 10 and 20 μmol/L bicuculline (P<0.05). Conclusion Bicuculline can abolish GABAA receptor-mediated inlaibition and affect the excitatory postsynaptic potential in a dose-dependent manner, and at a critical level, bicuculline induces GABAergic disinhibition to result in enhanced LTP in hippocampal slices.%目的 研究改变中间神经元GABA能抑制水平对海马CA1区突触长时程增强(LTP)的影响.同时获得不同浓度Bicuculline阻断GABAA受体介导抑制以及影响海马CA1区突触可塑性详细信息. 方法 应用膜片钳全细胞记录技术记录成年小鼠海马脑片上自发的微小的抑制性突触后电位(mIPSC)和诱发的前馈抑制性突触后电流(IPSC),使用细胞外电生理方法 记录刺激Schaffer侧枝诱发的CA1区辐射层场的兴奋性突触后电位(fEPSP],测量不同浓度Bicuculline对mIPSC、IPSC和fEPSP的作用,以及它们对小鼠海马脑片CA1区突触LTP的影响. 结果 10μmol/L、20μmol/L Bicuculline可以减弱mIPSC和IPSC抑制性突触电流,且20 μmol/L Bicuculline作用更明显;20μmol/L Bicuculline可以明显提高fEPSP的斜率,而5 μmol/L和10 μmol/LBicuculline没有明显作用;5 μmol/L、10 μmol/L、20μmol/L和50μmol/L Bicuculline组100赫兹强直刺激诱发后的fEPSP平均斜率均值都大于对照组,但仅10 μmol/L、20 μmol/L两组相比,差异有统计学意义(P<0.05). 结论 Bicuculline可以减弱GABAA受体介导的抑制以及增加场的fEPSP斜率,并且Bicuculline阻断GABA能抑制到一个关键水平才可以增强海马CA1区突触的LTP.