Gabriel Siegrun, Njunting Marleisje, Pomper Joern K, Merschhemke Martin, Sanabria Emilio R G, Eilers Alexander, Kivi Anatol, Zeller Melanie, Meencke Heinz-Joachim, Cavalheiro Esper A, Heinemann Uwe, Lehmann Thomas-Nicolas
Johannes Mueller Institute of Physiology, D-10117 Berlin, Germany.
J Neurosci. 2004 Nov 17;24(46):10416-30. doi: 10.1523/JNEUROSCI.2074-04.2004.
Hippocampal specimens resected to cure medically intractable temporal lobe epilepsy (TLE) provide a unique possibility to study functional consequences of morphological alterations. One intriguing alteration predominantly observed in cases of hippocampal sclerosis is an uncommon network of granule cells monosynaptically interconnected via aberrant supragranular mossy fibers. We investigated whether granule cell populations in slices from sclerotic and nonsclerotic hippocampi would develop ictaform activity when challenged by low-frequency hilar stimulation in the presence of elevated extracellular potassium concentration (10 and 12 mm) and whether the experimental activity differs according to the presence of aberrant mossy fibers. We found that ictaform activity could be evoked in slices from sclerotic and nonsclerotic hippocampi (27 of 40 slices, 14 of 20 patients; and 11 of 22 slices, 6 of 12 patients, respectively). However, the two patient groups differed with respect to the pattern of ictaform discharges and the potassium concentration mandatory for its induction. Seizure-like events were already induced with 10 mm K+. They exclusively occurred in slices from sclerotic hippocampi, of which 80% displayed stimulus-induced oscillatory population responses (250-300 Hz). In slices from nonsclerotic hippocampi, atypical negative field potential shifts were predominantly evoked with 12 mm K+. In both groups, the ictaform activity was sensitive to ionotropic glutamate receptor antagonists and lowering of [Ca2+]o. Our results show that, in granule cell populations of hippocampal slices from TLE patients, high K+-induced seizure-like activity and ictal spiking coincide with basic electrophysiological abnormalities, hippocampal sclerosis, and mossy fiber sprouting, suggesting that network reorganization could play a crucial role in determining type and threshold of such activity.
为治疗药物难治性颞叶癫痫（TLE）而切除的海马标本为研究形态学改变的功能后果提供了独特的机会。在海马硬化病例中主要观察到的一种有趣改变是通过异常的颗粒上层苔藓纤维单突触互连的颗粒细胞罕见网络。我们研究了在细胞外钾浓度升高（10和12 mM）的情况下，当受到低频海马门区刺激时，硬化和非硬化海马切片中的颗粒细胞群体是否会产生癫痫样活动，以及实验活动是否因异常苔藓纤维的存在而不同。我们发现，硬化和非硬化海马切片中均可诱发癫痫样活动（分别为40个切片中的27个，20例患者中的14例；以及22个切片中的11个，12例患者中的6例）。然而，两组患者在癫痫样放电模式和诱发所需的钾浓度方面存在差异。10 mM K+即可诱发癫痫样事件。它们仅发生在硬化海马的切片中，其中80%表现出刺激诱发的振荡群体反应（250-300 Hz）。在非硬化海马的切片中，主要用12 mM K+诱发非典型负性场电位变化。在两组中，癫痫样活动对离子型谷氨酸受体拮抗剂和[Ca2+]o降低敏感。我们的结果表明，在TLE患者海马切片的颗粒细胞群体中，高钾诱导的癫痫样活动和癫痫样棘波与基本电生理异常、海马硬化和苔藓纤维发芽一致，表明网络重组可能在决定此类活动的类型和阈值方面起关键作用。
