Adaptive Intrinsic Plasticity in Human Dentate Gyrus Granule Cells during Temporal Lobe Epilepsy
Adaptive Intrinsic Plasticity in Human Dentate Gyrus Granule Cells during Temporal Lobe Epilepsy
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DOI：
10.1093/cercor/bhr294
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发表时间：
2012-09-01
期刊：
影响因子：
3.7
通讯作者：
Wolfart, Jakob
中科院分区：
文献类型：
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作者：
Stegen, Michael;Kirchheim, Florian;Wolfart, Jakob
齿状回中的颗粒细胞在体内只有稀疏的活性，并且在颞叶癫痫期间比邻近细胞更好地存活于海马硬化（HS）。这种现象可能与专门用于抵消激励的固有特性有关。我们使用癫痫手术中获得的急性海马脑片研究了人类颗粒细胞兴奋性的机制。膜片钳记录与药理学，免疫细胞化学和计算机模拟相结合。颗粒细胞的输入电阻与癫痫持续时间和HS程度呈负相关。超极化激活的ZD 7288敏感阳离子（I-H，HCN）电流和高度Ba 2+敏感的内向整流K+（Kir）电流（以及HCN 1和Kir2.2蛋白）在体树突上存在，并在重度HS患者中与轻度HS患者相比进一步增强。I-H的性质和功能在颗粒细胞中进行了表征。虽然I-H去极化的膜，它强烈地降低了输入电阻和移动的电流频率函数，以更高的输入值。HCN和Kir的分流影响是相似的，这些电导相关。未观察到共振。模拟表明，Kir和HCN电导的组合上调减弱兴奋性突触输入，同时稳定膜电位和响应性。因此，颗粒细胞在癫痫期间稳态地降低其输入-输出传递功能。
Granule cells in the dentate gyrus are only sparsely active in vivo and survive hippocampal sclerosis (HS) during temporal lobe epilepsy better than neighboring cells. This phenomenon could be related to intrinsic properties specifically adapted to counteract excitation. We studied the mechanisms underlying the excitability of human granule cells using acute hippocampal slices obtained during epilepsy surgery. Patch-clamp recordings were combined with pharmacology, immunocytochemistry, and computer simulations. The input resistance of granule cells correlated negatively with the duration of epilepsy and the degree of HS. Hyperpolarization-activated, ZD7288-sensitive cation (I-H, HCN) currents and highly Ba2+-sensitive, inwardly rectifying K+ (Kir) currents (and HCN1 and Kir2.2 protein) were present somatodendritically and further enhanced in patients with severe HS versus mild HS. The properties and function of I-H were characterized in granule cells. Although I-H depolarized the membrane, it strongly reduced the input resistance and shifted the current-frequency function to higher input values. The shunting influence of HCN and Kir was similar and these conductances correlated. Resonance was not observed. Simulations suggest that the combined upregulation of Kir and HCN conductances attenuates excitatory synaptic input, while stabilizing the membrane potential and responsiveness. Thus, granule cells homeostatically downscale their input-output transfer function during epilepsy.