Artikel
Mossy fibres innervate excitatory granule cells and inhibitory basket cells in hippocampi of patients with temporal lobe epilepsy
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Veröffentlicht: | 8. Juni 2016 |
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Gliederung
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Objective: Temporal lobe epilepsy is frequently associated with hippocampal sclerosis, characterised by a selective loss of mossy cells in the hilus and of pyramidal cells in CA1. Granule cells survive, but their axons, the mossy fibres, sprout backwards to the granule cell layer, because they have lost the mossy cells as target cells, through mossy cell death. It has been suggested so far, that this leads to excitatory circuits. We examined whether sprouted mossy fibres impinge only excitatory granule cells or also inhibitory interneurons such as basket cells, which might be present in a smaller number.
Method: Resected hippocampal specimens of patients with temporal lobe epilepsy were compared with control hippocampi of patients with temporal lobe lesions, which showed only mild hippocampal sclerosis. 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 GABA-immunogold.
Results: We found, that sprouted mossy fibres of epileptic hippocampi innervate not only excitatory granule cells but also inhibitory parvalbuminergic interneurons, as basket cells. Further we observed, that the axonal plexus of inhibitory basket cells, which surrounds the granule cells, was preserved in hippocampal sclerosis. We quantified the connections of sprouted mossy fibres with the inhibitory axonal plexus and showed that the number of persisting inhibitory axon terminals exceeds significantly the number of newly sprouted excitatory mossy fibre terminals.
Conclusions: We conclude that this might lead to an increased inhibition and synchronisation of granule cells because the preserved basket cells show an additional innervation through sprouted mossy fibres, which results in an instability of a previously balanced network.