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The Journal of Neuroscience, November 17, 2004, 24(46):10416-10430; doi:10.1523/JNEUROSCI.2074-04.2004
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Neurobiology of Disease
Stimulus and Potassium-Induced Epileptiform Activity in the Human Dentate Gyrus from Patients with and without Hippocampal Sclerosis
Siegrun Gabriel,1 *
Marleisje Njunting,1 *
Joern K. Pomper,1
Martin Merschhemke,3
Emilio R. G. Sanabria,4
Alexander Eilers,1
Anatol Kivi,1
Melanie Zeller,1
Heinz-Joachim Meencke,3
Esper A. Cavalheiro,4
Uwe Heinemann,1 and
Thomas-Nicolas Lehmann1,2
1Johannes Mueller Institute of Physiology, D-10117 Berlin, Germany, 2Department of Neurosurgery, Charité-University Medicine Berlin, D-13353 Berlin, Germany, 3Epilepsy Center of Berlin and Brandenburg, Evangelisches Krankenhaus Königin Elisabeth Herzberge, D-10362 Berlin, Germany, and 4Laboratorio de Neurologia Experimental, Universidade Federal de Sao Paulo-Escola Paulista de Medicina, 04023-900 Sao Paulo, Brazil
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.
Key words: hippocampus; Ammon's horn sclerosis; mesial temporal lobe epilepsy; mossy fiber sprouting; high potassium; bicuculline; ictaform events
Received Oct 3, 2003;
revised August 28, 2004;
accepted October 2, 2004.
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