Abstracts

Rationale: The adrenergic system has been shown to exhibit robust antiepileptic properties without negative effects on learning and memory as often experienced with many antiepileptic therapies. This makes exploitation of adrenergic mechanisms a prime target for new antiepileptic treatments. Integral in learning and memory processes, hippocampal CA3 pyramidal cells are a common focus in temporal lobe epilepsy. We have previously identified an α_2A AR mediated response on hippocampal CA3 pyramidal neurons which robustly inhibits CA3 epileptiform activity. We hypothesize that this receptor inhibits epileptiform activity by disrupting the recurrent excitatory drive between CA3 cells.Methods: Pharmacological and surgical isolation techniques were used to examine the cell type responsible for this αAR response. Using whole-cell recordings in rat hippocampal slices, we examined excitatory post synaptic potential’s (EPSC’s), a measure of synaptic strength, evoked from the major connections of the CA3 pyramidal neurons to further localize this adrenergic effect.Results: Pharmacological and surgical isolation localized this response to the CA3 pyramidal cells themselves. Preliminary evidence suggests that only recurrent CA3 synapses are inhibited by α₂ stimulation, while the excitatory drive to and from the CA3 cells is not inhibited. Conclusions: Overexcitation of CA3 recurrent synapses is thought to be a primary cause in temporal lobe seizures. Since this α₂AR response is specific to CA3 recurrent synapses, this may explain how the adrenergic system may be antiepileptic while at the same time not affecting other areas of cognitive function such as learning or memory. (This study was funded by the Epilepsy Foundation (CWDJ), North Dakota EPSCoR through NSF grant EPS-0447679 (VAD), NSF CAREER award 0347259 (VAD), and NIH grant 5P20RR017699 from the COBRE program (VAD)).