Abstracts

Rationale: The ventrolateral PAG is a brainstem region that is a critical site in the neuronal network for audiogenic seizures (AGS) in genetically epilepsy-prone rats (GEPR-9s). The requisite neuronal network for AGS in GEPR-9s is restricted to brainstem structures, and no forebrain sites are required. Periodic repetition of AGS in GEPR-9s results in AK, which mimics human generalized tonic-clonic seizure in that tonic seizures are followed by generalized post-tonic clonus (PTC). The neuronal network for kindled AGS expands to include forebrain sites, particularly the amygdala, which is a critical site for PTC. Pathways from the amygdala to PAG are well documented. The PTC behavior induced by AK may involve a re-entry of AGS activity from the amygdala to PAG, and the present study examined if changes in this pathway were involved in the mechanisms of epileptogenesis that mediate AK. Methods: GEPR-9s (200-300 gm) were subjected to the AK paradigm involving 14 AGS (122 dB SPL, re: 0.0002 dyne/cm², induced with an electrical bell ) over a 7 day period. Under ketamine/xylazine anesthesia a stimulation electrode was implanted in central amygdala and microwire recording electrodes were implanted to record single unit neuronal firing. At least one week after surgery extracellular action potential responses in PAG neurons to electrical stimuli (100-200 A, 1 msec pulses) in the amygdala were examined in freely moving unanesthetized GEPR-9s. Stimulus response curves were compared in AK and non-kindled GEPR-9s. Results: PAG neuronal responsiveness to electrical stimuli in the amygdala exhibited increases with increasing stimulus intensity in non-kindled GEPR-9s. However, in GEPR-9s subjected to AK, the firing increase was consistently greater than the levels in non-kindled rats. Thus, in non-kindled GEPR-9s the electrically-evoked action potentials showed a significant increase at 100, 150 and 200 A. In the GEPR-9s subjected to AK, the mean number of action potentials evoked by amygdala stimulation was greater at all intensities, reaching statistical significance at 150 A. Conclusions: The results indicate that consistent PAG neuronal responses were evoked by electrical stimulation in the amygdala, which showed an intensity-related increase in GEPR-9s. GEPR-9s subjected to AK showed greater responsiveness in this pathway, suggesting that AK involves plastic changes in this pathway. This plasticity may be an important mechanism of epileptogenesis that mediates the emergence of PTC induced by AK. (Support: EAM and SIUSM Funds)