Artikel
Connectivity of the hippocampal mossy fibre system in patients with temporal lobe epilepsy
Neuronale Verbindung des Moosfasersystems im Hippocampus von Patienten mit Temporallappenepilepsie
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Veröffentlicht: | 8. Mai 2006 |
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Objective: Temporal lobe epilepsy is frequently associated with Ammon’s horn sclerosis which is characterised by neuronal death and sclerosis in the hippocampal regions CA1 and hilus. Additionally, there is a reorganisation of mossy fibres in the dentate gyrus, known as mossy fibre sprouting. This sprouting is characterised by an abnormal projection of granule cell axon collaterals backwards to the granule cell layer. It has been proposed that sprouting contributes to seizure generation by forming a local excitatory feedback circuit of granule cells. However, data obtained in animal models show also a connection of sprouted mossy fibres with inhibitory basket cells.
Methods: We examined the connectivity of mossy fibres in neurosurgical specimens of patients with temporal lobe epilepsy using a novel tracing technique. In addition, double immunolabeling and electron microscopy were applied to identify putative target cells of the sprouting mossy fibres.
Results: We have shown that excitatory granule cell axons (mossy fibres) impinge both on excitatory granule cells and inhibitory interneurons. Granule cells were identified by direct tracer application and synaptoporin IHC; inhibitory interneurons (basket cells) were identified by parvalbumin IHC and GABA-postembedding immunogold electron microscopy.
Conclusions: These results suggest that backsprouted mossy fibres do not only lead to an excitatory feedback circuit but also innervate inhibitory basket cells. We hypothesise that this aberrant innervation of interneurons not only results in an increased inhibition of dentate granule cells, but may contribute to the synchronisation of this network.
Supported by the Deutsche Forschungsgemeinschaft: TR-3 and Graduiertenkolleg 843