gms | German Medical Science

Objective: Temporal lobe epilepsy is characterized by a sclerosis of the hippocampus (Ammon’s horn sclerosis) with a specific loss of pyramidal cells in CA1 and mossy cells in the hilus. Excitatory granule cells survive, but show a reorganization of their axonal connections. Their axons, the mossy fibres, loose their target cells due to mossy cell death and sprout backwards into the granule cell layer. It was suggested so far, that this leads to a recurrent, excitatory circuit. The aim of this study was to examine the target cells of mossy fibre sprouting, and determine whether mossy fibres impinge only on granule cells or also on other neurons, in particular inhibitory interneurons (basket cells).

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

Results: In human epileptic hippocampi sprouted mossy fibres innervated not only excitatory granule cells but also inhibitory interneurons. In addition, we show that the inhibitory axonal plexus around granule cells is preserved and that the number of inhibitory axon terminals exceeds the number of excitatory sprouted mossy fibre terminals on granule cells.

Conclusions: Sprouting of mossy fibres does not simply results in an excitatory circuit of granule cells because recurrent mossy fibres also innervate inhibitory interneurons. This might lead to increased inhibition and synchronization of granule cells because the extensive inhibitory axonal plexus is preserved and shows an additional innervation through sprouted mossy fibres.