gms | German Medical Science

62nd Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Polish Society of Neurosurgeons (PNCH)

German Society of Neurosurgery (DGNC)

7 - 11 May 2011, Hamburg

Mossy fiber sprouting in hippocampi of patients with temporal lobe epilepsy creates an inhibitory neuronal feedback circuit

Meeting Abstract

  • T.M. Freiman - Abteilung Allgemeine Neurochirurgie, Universitätsklinikum Freiburg
  • C.A. Haas - AG Experimentelle Epilepsieforschung, Abteilung Allgemeine Neurochirurgie, Universitätsklinikum Freiburg
  • M. Frotscher - Abteilung für Neuroanatomie, Institut für Anatomie und Zellbiologie, Albert-Ludwigs-Universität Freiburg
  • J. Zentner - Abteilung Allgemeine Neurochirurgie, Universitätsklinikum Freiburg

Deutsche Gesellschaft für Neurochirurgie. Polnische Gesellschaft für Neurochirurgen. 62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH). Hamburg, 07.-11.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. DocP 065

DOI: 10.3205/11dgnc286, URN: urn:nbn:de:0183-11dgnc2866

Published: April 28, 2011

© 2011 Freiman et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

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Objective: Temporal lobe epilepsy is characterized by sclerosis of the hippocampus (Ammon’s horn sclerosis) with a specific loss of neurons in the subregions CA1 and in the hilus. In contrast, excitatory granule cells survive, but show a reorganization of their axonal connections. Their axons, the mossy fibers, sprout backwards to the granule cell layer and it has been suggested that this leads to an excitatory circuit. However, electrophysiological recordings surprisingly showed no increased excitation. The aim of this study was to examine the target cells of mossy fiber sprouting and to determine whether mossy fibers impinge only granule cells or also other neurons, in particular inhibitory interneurons (basket cells).

Methods: Mossy fibers were traced with neurobiotin. In addition, double immunohistochemistry against synaptoporin (mossy fibers) and parvalbumin (basket cells) was used. Synapses were examined with electron microscopy, labelled with post-embedding gamma-aminobutyric-acid (GABA)-immunogold in addition.

Results: We demonstrated that sprouted mossy fibers in human epileptic hippocampi not only innervated excitatory granule cells but also impinged inhibitory basket cells, which showed immunoreactivity against GABA and parvalbumin. In addition it was shown that the inhibitory axonal plexus around the granule cells was still preserved.

Conclusions: Sprouting of mossy fibers does not simply result in an excitatory circuit of granule cells because mossy fibers also innervate inhibitory interneurons. This leads to an increased inhibition and synchronisation of granule cells because the extensive inhibitory axonal plexus is preserved and even shows additional increased innervation through back-sprouted mossy fibers.

Supported by the Deutsche Forschungsgemeinschaft: Transregio-Sonderforschungsbereich 3