High ratio of synaptic excitation to synaptic inhibition in hilar ectopic granule cells of pilocarpine-treated rats.
High ratio of synaptic excitation to synaptic inhibition in hilar ectopic granule cells of pilocarpine-treated rats.
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DOI：
10.1152/jn.00663.2010
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发表时间：
2010-09
影响因子：
2.5
通讯作者：
Ren-Zhi Zhan;O. Timofeeva;J. V. Nadler;Ren-Zhi Zhan;Timofeeva O Nadler;Jv High;J. V. Nadler
中科院分区：
文献类型：
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作者：
Ren-Zhi Zhan;O. Timofeeva;J. V. Nadler;Ren-Zhi Zhan;Timofeeva O Nadler;Jv High;J. V. Nadler
实验性癫痫持续状态后，许多在癫痫发作后环境中产生的齿状颗粒细胞异常迁移到齿状门。在癫痫患者中也发现了肺门异位颗粒细胞（HEGC）。这些细胞表现出高自发活动率，这可能会增强癫痫发作的传播。电子显微镜研究表明，在同一动物中，HEGC 比正常颗粒细胞接受更多的周期性苔藓纤维神经支配，但接受的抑制性神经支配要少得多。本研究使用经历过毛果芸香碱诱导的癫痫持续状态的大鼠制备的海马切片来检验突触兴奋和抑制的不平衡导致 HEGC 过度兴奋的假设。与对照大鼠或经历过癫痫持续状态的大鼠的正常位颗粒细胞相比，苔藓纤维刺激在 HEGC 中引起的 GABA(A) 受体介导的抑制性突触后电流 (IPSC) 要小得多。然而，在经历过癫痫持续状态的大鼠中，HEGC 和正常位颗粒细胞记录了大小相似的反复苔藓纤维诱发的兴奋性突触后电流 (EPSC)。在所有颗粒细胞组中，HEGC 表现出最高频率的微型兴奋性突触后电流 (mEPSC) 和最低频率的微型抑制性突触后电流 (mIPSC)。平均而言，与对照大鼠的颗粒细胞相比，HEGC 中的 mEPSC 和 mIPSC 均具有更高的振幅，每个事件转移更多的电荷，并且表现出更慢的动力学。与正常颗粒细胞组相比，HEGC 中单位时间的电荷转移，mEPSC 更大，而 mIPSC 则少得多。兴奋性与抑制性突触功能的高比例可能部分解释了 HEGC 的过度兴奋性。
After experimental status epilepticus, many dentate granule cells born into the postseizure environment migrate aberrantly into the dentate hilus. Hilar ectopic granule cells (HEGCs) have also been found in persons with epilepsy. These cells exhibit a high rate of spontaneous activity, which may enhance seizure propagation. Electron microscopic studies indicated that HEGCs receive more recurrent mossy fiber innervation than normotopic granule cells in the same animals but receive much less inhibitory innervation. This study used hippocampal slices prepared from rats that had experienced pilocarpine-induced status epilepticus to test the hypothesis that an imbalance of synaptic excitation and inhibition contributes to the hyperexcitability of HEGCs. Mossy fiber stimulation evoked a much smaller GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSC) in HEGCs than in normotopic granule cells from either control rats or rats that had experienced status epilepticus. However, recurrent mossy fiber-evoked excitatory postsynaptic currents (EPSCs) of similar size were recorded from HEGCs and normotopic granule cells in status epilepticus-experienced rats. HEGCs exhibited the highest frequency of miniature excitatory postsynaptic currents (mEPSCs) and the lowest frequency of miniature inhibitory postsynaptic currents (mIPSCs) of any granule cell group. On average, both mEPSCs and mIPSCs were of higher amplitude, transferred more charge per event, and exhibited slower kinetics in HEGCs than in granule cells from control rats. Charge transfer per unit time in HEGCs was greater for mEPSCs and much less for mIPSCs than in the normotopic granule cell groups. A high ratio of excitatory to inhibitory synaptic function probably accounts, in part, for the hyperexcitability of HEGCs.