Excitatory and inhibitory postsynaptic currents in a rat model of epileptogenic microgyria
Excitatory and inhibitory postsynaptic currents in a rat model of epileptogenic microgyria
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DOI：
10.1152/jn.00288.2004
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发表时间：
2005-02-01
影响因子：
2.5
通讯作者：
Prince, DA
中科院分区：
文献类型：
--
作者：
Jacobs, KM;Prince, DA
发育性皮质畸形在难治性癫痫患者中很常见;然而，目前对导致癫痫发生的机制知之甚少。我们以前的特点是过度兴奋的大鼠模型，模仿人类4层microgyria的组织病理学。在这里，我们研究了抑制性和兴奋性突触后电流在这个模型中，以确定功能的改变，可能有助于癫痫相关的小脑回。我们记录了分离的全细胞兴奋性突触后电流和GABA（A）受体介导的抑制性电流（EPSC和IPSC）的第V层锥体神经元在该地区以前被证明是癫痫（旁微回区）和在同位控制皮层。局部刺激60%的PMG细胞可诱发癫痫样活动。与对照组相比，所有PMG细胞的自发和诱发IPSC的峰值电导均显着较大。在阻断亲离子性突触能电流或微型（m）IPSC后，振幅的这种差异不存在，表明这是由于兴奋性传入活动驱动抑制性神经元所致。与对照细胞相比，谷氨酸受体拮抗剂应用导致一个PMG细胞组（PMG（E））中自发IPSC频率显著更大的降低，这一发现支持了这一结论。在所有PMG细胞中，自发和微型EPSC的频率都显著更高，这表明与微回相邻的锥体神经元比控制皮层中的神经元接收更多的兴奋性输入。这些研究结果表明，有一个功能兴奋性突触的数量增加，中间神经元和锥体细胞在PMG皮质可能是由于hyperneurvation皮质传入最初注定的微回适当。
Developmental cortical malformations are common in patients with intractable epilepsy; however, mechanisms contributing to this epileptogenesis are currently poorly understood. We previously characterized hyperexcitability in a rat model that mimics the histopathology of human 4-layered microgyria. Here we examined inhibitory and excitatory postsynaptic currents in this model to identify functional alterations that might contribute to epileptogenesis associated with microgyria. We recorded isolated whole cell excitatory postsynaptic currents and GABA(A) receptor-mediated inhibitory currents (EPSCs and IPSCs) from layer V pyramidal neurons in the region previously shown to be epileptogenic (paramicrogyral area) and in homotopic control cortex. Epileptiform-like activity could be evoked in 60% of paramicrogyral (PMG) cells by local stimulation. The peak conductance of both spontaneous and evoked IPSCs was significantly larger in all PMG cells compared with controls. This difference in amplitude was not present after blockade of ionotropic glutamatergic currents or for miniature (m)IPSCs, suggesting that it was due to the excitatory afferent activity driving inhibitory neurons. This conclusion was supported by the finding that glutamate receptor antagonist application resulted in a significantly greater reduction in spontaneous IPSC frequency in one PMG cell group (PMG(E)) compared with control cells. The frequency of both spontaneous and miniature EPSCs was significantly greater in all PMG cells, suggesting that pyramidal neurons adjacent to a microgyrus receive more excitatory input than do those in control cortex. These findings suggest that there is an increase in numbers of functional excitatory synapses on both interneurons and pyramidal cells in the PMG cortex perhaps due to hyperinnervation by cortical afferents originally destined for the microgyrus proper.