Delayed development of spontaneous seizures and prolonged convulsive state in rats after massed stimulation of the anterior piriform cortex

We studied the short- and long-term epileptogenic effects of massed stimulation (MS) of the piriform cortex. Sprague-Dawley rats with electrodes implanted bilaterally in the anterior piriform cortex and the dorsal and ventral hippocampi underwent MS: electrical stimulation of the left piriform cortex every 5 min for 6 h (afterdischarge threshold, 60 Hz, 1 ms, 1 s). Animals were retested (5 stimulations) 3-4 times later at different time points to check for the kindled state. Our data showed that MS resulted in delayed development of severe epilepsy. The interval between MS and the first appearance of convulsive response (2 weeks) was characterized by deep refractoriness to seizure (silent period). Unexpectedly, dramatic seizure activity occurred 4-7 weeks after MS. This was manifested by (1) generalized tonic-clonic convulsions with multiple failings, which were elicited repeatedly during retest; (2) frequent progression of elicited generalized convulsions into a prolonged (> 8 min) postictal convulsive state expressed mainly by continuous partial seizures and even new bouts of generalized seizures, and (3) development of mild spontaneous seizures. We found that epileptiform activity predominated in the ventral hippocampus. Mossy fiber sprouting was also most pronounced in this area. We propose that the MS resulted in formation of pathological circuits which involve both piriform cortex and ventral hippocampus and lead to severe epilepsy.