- Injection of 0.2–3.0 ng of tetanus toxin into rat parietal neocortex resulted in permanent (> 7 months) changes in the local circuit properties of this tissue. It caused excessive synchronization of neuronal activity. This was seen as spontaneous paroxysmal field potentials and/or evoked all-or-none population burst discharges. Such activity was recorded widely over the parietal and temporal areas of both the injected and the contralateral hemispheres from as little as 16 h after injection up to the maximum survival time of 7 months. Several observations suggest that the speed with which the hypersynchronous activity spread to the opposite hemisphere reflects transport of the toxin through corticocortical axons, and consequent blockade of synaptic inhibition. However, from what is known of the half life of the peptide in brain, it is unlikely that the persistent, widespread distribution of epileptiform discharge several months after injection was due to the continued presence of toxin. Thus, intracortical application of tetanus toxin provides a good experimental model of chronic focal epilepsies, and raises fundamental questions regarding the long term regulation of local circuit properties in the neocortex.