Effects of Levetiracetam on granule cells and fast spikeing basket cells in the dentate gyrus

Abstract

Event Abstract Back to Event Effects of Levetiracetam on granule cells and fast spikeing basket cells in the dentate gyrus Stefan Hefft1*, Stefanie Heigele1, Gerd Münzner1, Andreas Schulze-Bonhage1 and Ad Aertsen2 1 Freiburg University, Germany 2 BCCN, Germany Levetiracetam (LEV) is one of the most important antiepileptic drugs commonly used in clinical practice. Although binding studies have shown that LEV interacts with the synaptic vesicle proteine 2A (SV2A), it's mechanism of action has largely remained unknown. Furthermore, experimental data have also shown small effects on voltage-gated ion channels. Here we used mainly transverse hippocampal slices of juvenile rats (P17-P22) in order to study the electrophysiological effects of the active enantiomer of LEV (100 μM) on granule cells (GCs) and fast spiking basket cells (BCs) in the dentate gyrus (DG)at room temperature. Current clamp recordings in both cell types show no effect on resting membrane conductance, de- and re-polarization kinetics of action potential waveforms, afterde- or afterhyper-polarization potentials, input-output curves, constructed by 1 second lasting constant current injections ( -0,1 to 1-1,2 nA) or bursting patterns induced by short, depolarizing current pulses in both GCs and BCs. These data argue against a significant physiological effect of LEV through voltage-gated channels. However, preliminary data show a reduction of spontaneous IPSC amplitudes recorded in GCs. Importantly, this effect was reversible, and its time course was compatible with the onset of the effect of LEV seen upon intravenously applied drug in epileptic patients. Thus, fine-tuning of GABAergic inhibitory transmission may be the main effect of LEV. In the next step, we will now repeat these experiments in human tissue and thereafter integrate the data in a simple neuronal network in order to perform a computational analysis of the effects of LEV on ictogenesis. Conference: Bernstein Symposium 2008, Munich, Germany, 8 Oct - 10 Oct, 2008. Presentation Type: Poster Presentation Topic: All Abstracts Citation: Hefft S, Heigele S, Münzner G, Schulze-Bonhage A and Aertsen A (2008). Effects of Levetiracetam on granule cells and fast spikeing basket cells in the dentate gyrus. Front. Comput. Neurosci. Conference Abstract: Bernstein Symposium 2008. doi: 10.3389/conf.neuro.10.2008.01.058 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 16 Nov 2008; Published Online: 16 Nov 2008. * Correspondence: Stefan Hefft, Freiburg University, Freiburg, Germany, stefan.hefft@uniklinik-freiburg.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Stefan Hefft Stefanie Heigele Gerd Münzner Andreas Schulze-Bonhage Ad Aertsen Google Stefan Hefft Stefanie Heigele Gerd Münzner Andreas Schulze-Bonhage Ad Aertsen Google Scholar Stefan Hefft Stefanie Heigele Gerd Münzner Andreas Schulze-Bonhage Ad Aertsen PubMed Stefan Hefft Stefanie Heigele Gerd Münzner Andreas Schulze-Bonhage Ad Aertsen Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.