Kindling of neuroanatomic pathways during recurrent focal penicillin seizures.

Sequential changes in convulsive phenomena have been studied using intracortical injections of penicillin as a kindling agent. Rats given 25 units of penicillin every 4 days had a progressive increase in the frequency of contralateral muscle jerks. Unilateral tonic-clinic events began after the third injection, and bilateral jerks of both upper extremities began subsequent to that. No generalized convulsions occurred, and further changes in focal convulsions stopped after 7 injections. The seizure events occurring in this kindled state could be seen in rats given a single injection of 100 units of penicillin. Rats subjected to daily injections at this dosage did not develop more intense seizures, and afterdischarges essentially stopped after the first injection. Animals studied with deoxyglucose autoradiography during kindling with 25 units showed an increase in the size and intensity of metabolic activity in the seizure focus. In addition there was an increase in size and intensity of most transynaptic sites, with new activity appearing in contralateral basal ganglia. A comparison of these findings with the autoradiographic results of animals receiving 100 units of penicillin suggests that the major change during kindling takes place in the focus itself. The appearance of new activity in contralateral basal ganglia is probably an expression of activity in crossed corticostriate pathways from the focus as well as pathways descending from the homotopic cortex in an obligatory input-output response. Use of these pathways is not dependent on kindling, but is available on a first come basis if the intensity of discharges from the seizure focus is strong enough.