Presynaptic Inhibitory Terminals Are Functionally Abnormal in a Rat Model of Posttraumatic Epilepsy
Presynaptic Inhibitory Terminals Are Functionally Abnormal in a Rat Model of Posttraumatic Epilepsy
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DOI：
10.1152/jn.00351.2010
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发表时间：
2010-07-01
影响因子：
2.5
通讯作者：
Prince, David A.
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文献类型：
--
作者：
Faria, Leonardo C.;Prince, David A.
Faria LC，Prince DA.大鼠创伤后癫痫模型中突触前抑制性终末功能异常。J Neurophysiol 104：280-290，2010.首次发表于2010年5月19日; doi：10.1152/jn.00351.2010。部分孤立的“底切”新皮层与完整的软脑膜循环是一个公认的模型创伤后癫痫。先前的实验结果表明，在第V层锥体（Pyr）神经元的底切的微型抑制性突触后电流（mIPSC）的频率降低。我们进一步研究了可能的功能异常，GABA能抑制大鼠致痫性新皮层切片在体外通过记录全细胞单突触IPSC层V Pyr细胞和快速尖峰（FS）GABA能中间神经元使用配对脉冲范例。与对照组相比，损伤脑片Pyr神经元的IPSC显示阈值增加，阈值峰值幅度降低，输入/输出斜率降低，失败率增加，配对脉冲抑制向配对脉冲易化（增加配对脉冲比或PPR）转变。增加[Ca 2 +]（0）从2到4毫米部分逆转这些异常的Pyr细胞的癫痫组织。FS细胞上的IPSC也具有增加的PPR和失败。阻断GABA（B）受体不影响配对结果。这些结果表明，有GABA能突触前末梢的Pyr和FS细胞在这个模型中的创伤后癫痫的功能改变。
Faria LC, Prince DA. Presynaptic inhibitory terminals are functionally abnormal in a rat model of posttraumatic epilepsy. J Neurophysiol 104: 280-290, 2010. First published May 19, 2010; doi:10.1152/jn.00351.2010. 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 [Ca2+](0) 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.