gms | German Medical Science

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