Abstracts

Transfer occurs when kindling of a site reduces the number of stimulations required to kindle subsequently from a secondary site. One explanation of transfer is that kindling of the first site causes other regions to become more susceptible to seizures. Typically only the rate of seizure generalization is affected in transfer, and parameters such as the afterdischarge (AD) threshold in the secondary site are unaltered.
It has been reported that prekindling of some brainstem sites results in transfer to forebrain sites, associated with development of classic AD in the brainstem. In our previous studies of brainstem kindling, we observed low amplitude high frequency tightly organized AD, not classic AD. Therefore, we examined the effects of prekindling the brainstem on secondary-site kindling of forebrain sites, to determine whether transfer requires triggering of classic AD in the primary site., Male Long-Evans rats carried bipolar electrodes aimed at the nucleus reticularis pontis oralis (RPO), mesencephalic reticular formation (MRF), dorsal periaqueductal grey (dPAG), or ventrolateral periaqueductal grey (vlPAG), with a second electrode aimed at the amygdala. AD thresholds were determined at the brainstem electrode, and the rats received 1-sec trains of balanced square wave stimulation once daily for 30 days.
Seven weeks after brainstem kindling the AD threshold of the amygdala was determined. Rats sham-kindled during the 30 days of brainstem stimulation served as the control group.
The experimental and control groups were stimulated in the amygdala at AD threshold twice daily, until they had five Stage 5 seizures or until they received 50 stimulations. Twenty-four hr after the last kindling session the AD thresholds were again measured., Prekindling of the RPO, vlPAG and MRF failed to produce transfer to the forebrain, in that kindling at the amygdala proceeded at the rate seen in naive control rats. However, prekindling of the dPAG produced positive transfer to amygdaloid kindling. Unexpectedly, all rats that were prekindled in brainstem sites failed to display a decrease in amygdaloid AD threshold when subsequently subjected to secondary-site kindling of the amygdala, in contrast to the significant decrease in amygdaloid AD threshold displayed by control rats., Our results suggest that prestimulation of brainstem sites results in inhibitory effects on forebrain kindling. The effects are not due to suppression of forebrain-triggered discharge and propagation to distal sites, but reflect inhibition of amygdaloid sensitization to the kindling stimulus. Because brainstem kindling involves low-voltage tightly organized AD, the triggering of classic AD in the brainstem during prekindling is not required for transfer to occur (i.e., dPAG group). Whether primary forebrain kindling affects subsequent brainstem kindling remains to be determined., (Supported by Grants from NSERC and CIHR to MEC.)