The effects of tetanus toxin (TeNT) both in the\nspinal cord, in clinical tetanus, and in the brain, in experimental\nfocal epilepsy, suggest disruption of inhibitory\nsynapses. TeNT is a zinc protease with selectivity for\nVesicle Associated Membrane Protein (VAMP; previously\nsynaptobrevin), with a reported selectivity for VAMP2 in\nrats. We found spatially heterogeneous expression of\nVAMP1 and VAMP2 in the hippocampus. Inhibitory terminals\nin stratum pyramidale expressed significantly more\nVAMP1 than VAMP2, while glutamatergic terminals in\nstratum radiatum expressed significantly more VAMP2\nthan VAMP1. Intrahippocampal injection of TeNT at doses\nthat induce epileptic foci cleaved both isoforms in tissue\naround the injection site. The cleavage was modest at\n2 days after injection and more substantial and extensive at\n8 and 16 days. Whole-cell recordings from CA1 pyramidal\ncells close to the injection site, made 8ââ?¬â??16 days after\ninjection, showed that TeNT decreases spontaneous EPSC\nfrequency to 38 % of control and VAMP2 immunoreactive\naxon terminals to 37 %. In contrast, TeNT almost completely\nabolished both spontaneous and evoked IPSCs\nwhile decreasing VAMP1 axon terminals to 45 %. We\nconclude that due to the functional selectivity of the toxin\nto the relative sparing of excitatory synaptic transmission\nshifts the network to pathogenically excitable state causing\nepilepsy.
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