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Open Access 01-03-2015 | Original Article

Structural and functional substrates of tetanus toxin in an animal model of temporal lobe epilepsy

Authors: Alex S. Ferecskó, Premysl Jiruska, Lucy Foss, Andrew D. Powell, Wei-Chih Chang, Attila Sik, John G. R. Jefferys

Published in: Brain Structure and Function | Issue 2/2015

Abstract

The effects of tetanus toxin (TeNT) both in the spinal cord, in clinical tetanus, and in the brain, in experimental focal epilepsy, suggest disruption of inhibitory synapses. TeNT is a zinc protease with selectivity for Vesicle Associated Membrane Protein (VAMP; previously synaptobrevin), with a reported selectivity for VAMP2 in rats. We found spatially heterogeneous expression of VAMP1 and VAMP2 in the hippocampus. Inhibitory terminals in stratum pyramidale expressed significantly more VAMP1 than VAMP2, while glutamatergic terminals in stratum radiatum expressed significantly more VAMP2 than VAMP1. Intrahippocampal injection of TeNT at doses that induce epileptic foci cleaved both isoforms in tissue around the injection site. The cleavage was modest at 2 days after injection and more substantial and extensive at 8 and 16 days. Whole-cell recordings from CA1 pyramidal cells close to the injection site, made 8–16 days after injection, showed that TeNT decreases spontaneous EPSC frequency to 38 % of control and VAMP2 immunoreactive axon terminals to 37 %. In contrast, TeNT almost completely abolished both spontaneous and evoked IPSCs while decreasing VAMP1 axon terminals to 45 %. We conclude that due to the functional selectivity of the toxin to the relative sparing of excitatory synaptic transmission shifts the network to pathogenically excitable state causing epilepsy.

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Title: Structural and functional substrates of tetanus toxin in an animal model of temporal lobe epilepsy
Authors: Alex S. Ferecskó
Premysl Jiruska
Lucy Foss
Andrew D. Powell
Wei-Chih Chang
Attila Sik
John G. R. Jefferys
Publication date: 01-03-2015
Publisher: Springer Berlin Heidelberg
Published in: Brain Structure and Function / Issue 2/2015
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-013-0697-1

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Structural and functional substrates of tetanus toxin in an animal model of temporal lobe epilepsy

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