Septotemporal position in the hippocampal formation determines epileptic activity in Temporal Lobe Epilepsy
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1
University of Freiburg, Department of Neurosurgery, Germany
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2
University of Freiburg, Bernstein Center Freiburg, Germany
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3
University of Freiburg, Faculty of Biology, Germany
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4
University of Freiburg, Department of Microsystems Engineering-IMTEK, Faculty of Engineering, Germany
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5
University of Freiburg, Department of Neurosurgery, Germany
Temporal Lobe Epilepsy (TLE) is associated with severe changes in cellular architecture of the hippocampus: cell loss in CA3, CA1 and the hilus, granule cell dispersion, mossy fiber sprouting, altered neurogenesis and gliosis. It is, however, still unclear how these changes contribute to the occurrence of epileptic seizures, in particular since some are supposed to have an anti-epileptic effect while others increase the excitability. In our approach, we characterize the strength and extent of epileptiform activity and then reconstruct the histological pattern at the respective positions along the septotemporal axis of the hippocampus to characterize potential interrelation.
To this end, we used the intrahippocampal kainate mouse epilepsy model, which recapitulates the main characteristics of TLE in humans: recurrent focal seizures, granule cell dispersion and selective cell death in the hippocampus. Following the focal injection of kainate into the hippocampus, we performed multi-site in vivo local field potential recordings along the septotemporal axis of the kainate-injected and in the contralateral hippocampus and quantified the strength of status epilepticus (SE) and recurrent epileptiform activity (EA). In addition, we used bromodeoxyuridine injections to monitor proliferative activity, immunohistochemistry and in situ hybridization to determine cell fate and interneuron loss and Nissl staining to measure granule cell dispersion and quantified all parameters.
We show that following kainate injection into the septal hippocampus, SE extended along the septotemporal axis of the hippocampus with stronger intensity at intermediate and temporal sites. Comparably, the intensity of recurrent EA was strongest in the intermediate hippocampus. The histological changes also showed septotemporal gradients: (1) Granule cell dispersion was strong in the septal hippocampus and ceased in the intermediate and temporal hippocampus. (2) Neurogenesis was completely lost in the septal hippocampus, but was strongly increased in the intermediate and temporal hippocampus. (3) Inhibitory interneurons were mostly lost in the septal hippocampus, still reduced in the intermediate hippocampus and back to normal numbers temporally. Notably, the site with strongest EA appeared to be the transition zone where neurogenesis reappeared but interneuron numbers were still reduced.
Therefore, we assume that the occurrence of strong EA requires increased excitation through the addition of hyperexcitable young granule cells and, in addition, decreased inhibition through the loss of inhibitory interneurons. In contrast, each change on its own has only minor effects.
Acknowledgements
Supported by the Deutsche Forschungsgemeinschaft (DFG, SFB TR3 and SFB780) and the Federal Ministry of Education and Research (BMBF FKZ 01GQ0420, 01GQ0830).
Keywords:
Epilepsy,
Epileptiform activity,
granule cells,
Hippocampus,
inhibition,
Interneurons,
Neurogenesis
Conference:
BC11 : Computational Neuroscience & Neurotechnology Bernstein Conference & Neurex Annual Meeting 2011, Freiburg, Germany, 4 Oct - 6 Oct, 2011.
Presentation Type:
Poster
Topic:
brain disease, network dysfunction and intervention (please use "brain disease, network dysfunction and intervention" as keyword)
Citation:
Häussler
U,
Marx
M,
Bielefeld
L,
Froriep
UP,
Wolfart
J and
Haas
CA
(2011). Septotemporal position in the hippocampal formation determines epileptic activity in Temporal Lobe Epilepsy.
Front. Comput. Neurosci.
Conference Abstract:
BC11 : Computational Neuroscience & Neurotechnology Bernstein Conference & Neurex Annual Meeting 2011.
doi: 10.3389/conf.fncom.2011.53.00222
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Received:
11 Aug 2011;
Published Online:
04 Oct 2011.
*
Correspondence:
Dr. Ute Häussler, University of Freiburg, Department of Neurosurgery, Freiburg, 79106, Germany, ute.haeussler@uniklinik-freiburg.de