INJECTION OF TETANUS TOXIN INTO THE NEOCORTEX ELICITS PERSISTENT EPILEPTIFORM ACTIVITY BUT ONLY TRANSIENT IMPAIRMENT OF GABA RELEASE

Focal injection of a minute quantity of tetanus toxin into the rat neo cortex induces chronic epileptogenesis. Within a day, spontaneous and stimulus-evoked paroxysmal discharges appear in widespread regions of both hemispheres and this lasts for at least nine months.6 Tetanus tox in blocks transmitter release, apparently by catalysing the breakdown of synaptobrevin, a synaptic protein.25 It specifically binds to neuro nal membranes32 but its potent epileptogenic properties have been ascr ibed to a higher affinity for inhibitory neurons.3,4,9,31 Following fo cal injection of tetanus toxin into the hippocampus a long-lasting epi leptic syndrome also develops.13,15,16 During the early part of the sy ndrome GABA release is depressed in slices from the injected side, but not in slices from the contralateral, secondary focus.11 In the prese nt experiments on neocortex, release of radiolabelled GABA was measure d from primary and secondary epileptic foci induced by unilateral foca l injection of tetanus toxin into the parietal cortex. By four weeks,a fter the injection, no differences were detected in GABA release from any neocortical site in control or toxin-injected animals, despite the persistence of profound epileptic activity in slices from the latter. At earlier times (1.5 days) after the toxin injection, however, relea se was significantly depressed in both hemispheres. The results indica te that at first, the toxin induces focal neocortical epileptogenesis by directly impeding GABAergic synaptic transmission but that with tim e there is a recovery from this initial effect. We propose, as has als o been suggested for other models,1,10,26,27 that the initial epilepto genesis leaves in its wake a long-lasting change in the local function al connectivity, such that the neocortex is rendered permanently epile ptic.