Previous studies have reported that the repetition of running-bouncing and
tonic-clonic seizures mediated by brainstem structures eventually elicits seizure activity in the forebrain. The purpose of the present study was to determine if the periaqueductal gray (PAG) region is a component of the neural network through which brainstem
seizures elicit forebrain
seizures. Bilateral microinjection of 40 nmol
carbachol into the PAG region of rats induced arrested, staring behavior accompanied by epileptiform electrocorticogram (ECoG) afterdischarge recorded from the parietal cortex. In two animals limbic seizure activity similar to kindled amygdala
seizures was also induced. The
carbachol effect was dose-related as the 40 nmol dose induced a significantly greater duration of ECoG afterdischarge than a 20 nmol dose. The
carbachol effect was mediated by
muscarinic receptors as bilateral 50 nmol
atropine microinjection 1 min prior to 40 nmol
carbachol microinjection inhibited all seizure activity. Immunohistochemical detection of the proto-oncogene c-fos was used to verify that seizure activity was induced in forebrain regions. Rats with
seizures induced by PAG
carbachol microinjections exhibited dense c-fos-like immunoreactivity in the dentate gyrus but not the CA(1) or CA(3) regions, amygdala, piriform cortex, perirhinal cortex or hypothalamus. In addition, PAG microinjection of 10 nmol
N-methyl-D-aspartic acid (
NMDA) induced wild-running convulsions while 400 pmol
bicuculline induced clonic
spasms, myoclonic activity or limbic
seizures. These results indicate that stimulation of the PAG, a brainstem structure, is sufficient to induce forebrain
seizures. Since the forebrain
seizures were induced by a single
carbachol administration, it is proposed that the PAG serves as a pathway for caudal-rostral seizure generalization.