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 Functional and structural alterations of GABAergic innervation in temporal lobe epilepsy


Inhibitory interneurons play a key role in chronic temporal lobe epilepsy (TLE). Several findings indicate that their power to balance out excitation might be reduced in TLE, which might cause or aggravate the seizure-susceptibility of the hippocampal-temporal lobe system. Attempts to measure the efficacy of GABA-mediated inhibition in animal models of TLE or in human tissue have yielded conflicting results, possibly due to the extreme heterogeneity of hippocampal interneurons and to the different conditions of tissue with and without Ammons horn sclerosis (AHS). In the current project we want to yield correlations between functional and anatomical alterations of the inhibitory interneurons in the hippocampus during TLE. We will employ one animal model with severe hippocampal cell loss (pilocarpine) and one model without AHS (kindling). Interneurons will be characterised electrophysiologically, with special respect to the balance between excitatory and inhibitory synaptic inputs. The data will be compared to data from confocal microscopical and ultrastructural studies which quantify the number of synapses on morphologically and histochemically identified interneurons. Similar and comparative morphological work will be performed on specimens from resected epileptic human hippocampus.

Collaboration:

Prof. Dr. A. Draguhn , Physiologisches Institut der Charité, Humboldt-Universität Berlin;
Prof. U. Heinemann, Physiologisches Institut der Charité, Humboldt-Universität Berlin;
Prof. Dr. B. Volk, I. Singec, Pathologisches Institut, Universität Freiburg;
PD. Dr. V. Schmieden, Physiologisches Institut der Charité, Humboldt-Universität Berlin

Supported by:

Transregionaler Sonderforschungsbereich SFB-TR 3 : Mesial Temporal Lobe Epilepsies Bonn - Berlin - Freiburg - Magdeburg, TP: B5

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