Spatial and temporal relationships between c-Fos expression and kindling of audiogenic seizures in Wistar rats

In a strain of Wistar rats selected in our laboratory, audiogenic seizures (AS), characterized by a wild running phase followed by a tonic seizure, ca n be elicited by exposure to sound. In these animals repeated daily stimula tions induce permanent changes which reflect the extension of seizure activ ity from the brainstem to the forebrain. C-Fos immunoreactivity was used to further characterize the sound-susceptibility of the strain and to specify the spatiotemporal relationships between c-Fos expression and development of AS kindling. AS susceptible rats appeared to be more sensitive to a subt hreshold sound as compared to controls. Sound-evoked wild running induced a similar pattern of c-Fos as a full AS in naive rats, confirming the epilep tic nature of this early component. AS-induced c-Fos labeling in the audito ry pathways of the brainstem extended to the forebrain with repetition of A S and marked increases in c-Fos expression sequentially occurred in the amy gdala and perirhinal cortex, followed by the frontoparietal cortex, the pir iform cortex, and finally the hippocampus and entorhinal cortex. These resu lts show that the kindled AS preferentially propagate from the brainstem, t hrough the amygdala and the perirhinal cortex, to the motor cortex, with th e piriform cortex and hippocampus as secondary targets. No more c-Fos expre ssion was detected 24 h after an AS. A down-regulation of cortical c-Fos in duction was observed 1 and 2 days after daily exposure to kindled AS, with full recovery of c-Fos expression after a 5-day seizure-free period. This s uggests a regulatory function of c-Fos expression in development of kindlin g, (C) 1999 Academic Press.