RT Journal Article
SR Electronic
T1 Stimulus and Potassium-Induced Epileptiform Activity in the Human Dentate Gyrus from Patients with and without Hippocampal Sclerosis
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 10416
OP 10430
DO 10.1523/JNEUROSCI.2074-04.2004
VO 24
IS 46
A1 Siegrun Gabriel
A1 Marleisje Njunting
A1 Joern K. Pomper
A1 Martin Merschhemke
A1 Emilio R. G. Sanabria
A1 Alexander Eilers
A1 Anatol Kivi
A1 Melanie Zeller
A1 Heinz-Joachim Meencke
A1 Esper A. Cavalheiro
A1 Uwe Heinemann
A1 Thomas-Nicolas Lehmann
YR 2004
UL http://www.jneurosci.org/content/24/46/10416.abstract
AB 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.