Preservation of perisomatic inhibitory input of granule cells in the epileptic human dentate gyrus

Preservation of perisomatic inhibitory input of granule cells in the epileptic human dentate gyrus
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DOI:
10.1016/s0306-4522(01)00446-8
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发表时间:
2001-01-01
期刊:
影响因子:
3.3
通讯作者:
Freund, TF
Freund, TF
中科院分区:
医学3区
文献类型:
--
作者:
Wittner, L;Maglóczky, Z;Freund, TF

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Temporal lobe epilepsy is known to be associated with hyperactivity that is likely to be generated or amplified in the hippocampal formation. The majority of granule cells, the principal cells of the dentate gyrus, Lire found to be resistant to damage in epilepsy. and may serve as generators of seizures if their inhibition is impaired. Therefore, the parvalbumin-containing subset of interneurons, known to provide the most powerful inhibitory input to granule cell somata and axon initial segments, were examined in human control and epileptic dentate gyrus. A strong reduction in the number of parvalbumin-containing cells was found in the epileptic samples especially in the hilar region, although in some patches of the granule cell layer parvalbumin-positive terminals that form vertical clusters characteristic of axoaxonic cells were more numerous than in controls. Analysis of the postsynaptic target elements of parvalbumin-positive axon terminals showed that they form symmetric synapses with somata, dendrites, axon initial segments and spines as in the control, but the ratio of axon initial segment synapses was increased in the epileptic tissue (control: 15.9%, epileptic: 31.3%). Furthermore. the synaptic coverage of granule cell axon initial segments increased more than three times (control: 0.52, epileptic: 2.10 mum synaptic length/100 mum axon initial segment membrane) in the epileptic samples, whereas the amount of somatic symmetric synapses did not change significantly. Although the number of parvalbumin-positive interneurons is decreased, the perisomatic inhibitory input of dentate granule cells is preserved in temporal lobe epilepsy. Basket and axo-axonic cell terminals - whether positive or negative for parvalbumin - are present, moreover, the axon collaterals targeting axon initial segments sprout in the epileptic dentate gyrus.We suggest that perisomatic inhibitory interneurons survive in epilepsy, but their somadendritic compartment and partly the axon loses parvalbumin or immunoreactivity for parvalbumin. The hyperinnervation of axon initial segments might be a compensatory change in the inhibitory network, but at the same time may lead to a more effective synchronization of granule cell firing that could contribute to the generation or amplification of epileptic seizures. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.