caa a22 4500 606203567 CHVBK 20210128100958.0 cr unu---uuuuu 210128e20150301xx s 000 0 eng 10.1007/s00429-013-0697-1 doi (NATIONALLICENCE)springer-10.1007/s00429-013-0697-1 Structural and functional substrates of tetanus toxin in an animal model of temporal lobe epilepsy [Elektronische Daten] [Alex Ferecskó, Premysl Jiruska, Lucy Foss, Andrew Powell, Wei-Chih Chang, Attila Sik, John Jefferys] 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 2days after injection and more substantial and extensive at 8 and 16days. Whole-cell recordings from CA1 pyramidal cells close to the injection site, made 8-16days 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. The Author(s), 2014 Epilepsy nationallicence Synaptic function nationallicence VAMP nationallicence Tetanus neurotoxin nationallicence Hippocampus nationallicence Ferecskó Alex Neuronal Networks Group, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, Birmingham, UK aut Jiruska Premysl Neuronal Networks Group, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, Birmingham, UK aut Foss Lucy Neuronal Networks Group, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, Birmingham, UK aut Powell Andrew Neuronal Networks Group, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, Birmingham, UK aut Chang Wei-Chih Neuronal Networks Group, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, Birmingham, UK aut Sik Attila Neuronal Networks Group, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, Birmingham, UK aut Jefferys John Neuronal Networks Group, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, Birmingham, UK aut Brain Structure and Function Springer Berlin Heidelberg 220/2(2015-03-01), 1013-1029 1863-2653 220:2<1013 2015 220 429 https://doi.org/10.1007/s00429-013-0697-1 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-013-0697-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ferecskó Alex Neuronal Networks Group, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, Birmingham, UK aut NATIONALLICENCE 700 1- Jiruska Premysl Neuronal Networks Group, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, Birmingham, UK aut NATIONALLICENCE 700 1- Foss Lucy Neuronal Networks Group, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, Birmingham, UK aut NATIONALLICENCE 700 1- Powell Andrew Neuronal Networks Group, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, Birmingham, UK aut NATIONALLICENCE 700 1- Chang Wei-Chih Neuronal Networks Group, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, Birmingham, UK aut NATIONALLICENCE 700 1- Sik Attila Neuronal Networks Group, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, Birmingham, UK aut NATIONALLICENCE 700 1- Jefferys John Neuronal Networks Group, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, Birmingham, UK aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/2(2015-03-01), 1013-1029 1863-2653 220:2<1013 2015 220 429