Department of Neurology and Neurological Sciences, School of Medicine, Stanford University, Stanford, California 94305-5122, USA.
J Neurophysiol. 2010 Jul;104(1):280-90. doi: 10.1152/jn.00351.2010. Epub 2010 May 19.
Partially isolated "undercut" neocortex with intact pial circulation is a well-established model of posttraumatic epileptogenesis. Results of previous experiments showed a decreased frequency of miniature inhibitory postsynaptic currents (mIPSCs) in layer V pyramidal (Pyr) neurons of undercuts. We further examined possible functional abnormalities in GABAergic inhibition in rat epileptogenic neocortical slices in vitro by recording whole cell monosynaptic IPSCs in layer V Pyr cells and fast-spiking (FS) GABAergic interneurons using a paired pulse paradigm. Compared with controls, IPSCs in Pyr neurons of injured slices showed increased threshold and decreased peak amplitude at threshold, decreased input/output slopes, increased failure rates, and a shift from paired pulse depression toward paired pulse facilitation (increased paired pulse ratio or PPR). Increasing Ca(2+) from 2 to 4 mM partially reversed these abnormalities in Pyr cells of the epileptogenic tissue. IPSCs onto FS cells also had an increased PPR and failures. Blockade of GABA(B) receptors did not affect the paired results. These findings suggest that there are functional alterations in GABAergic presynaptic terminals onto both Pyr and FS cells in this model of posttraumatic epileptogenesis.
部分隔离的“下切”皮质伴有完整的软脑膜循环是外伤性癫痫发生的成熟模型。先前的实验结果表明，下切皮质中 V 层锥体（Pyr）神经元的微小抑制性突触后电流（mIPSCs）频率降低。我们通过使用成对脉冲范式在体外记录 V 层 Pyr 细胞和快速放电（FS）GABA 能中间神经元的全细胞单突触 IPSC，进一步研究了大鼠癫痫性皮质切片中 GABA 能抑制的可能功能异常。与对照相比，损伤切片中 Pyr 神经元的 IPSC 显示出阈电位增加和阈电位下峰值幅度降低、输入/输出斜率降低、失败率增加，以及从成对脉冲抑制向成对脉冲易化（增加成对脉冲比或 PPR）的转变。将[Ca（2+）]（o）从 2mM 增加到 4mM 可部分逆转癫痫组织 Pyr 细胞中的这些异常。FS 细胞上的 IPSC 也具有增加的 PPR 和失败。GABA（B）受体阻断不影响配对结果。这些发现表明，在这种外伤性癫痫发生模型中，GABA 能突触前末梢对 Pyr 和 FS 细胞均存在功能改变。
