α adrenergic activation of GABAergic interneurons in region CA1 of the rat hippocampus

Heightened cellular activity in the hippocampus is implicated in a majority of temporal lobe epilepsies. In vitro, application of the catecholamine norepinephrine (NE) to hippocampal slices reduces experimentally‐induced seizure activity. We hypothesize NE exerts this antiepileptic effect in part through adrenergic activation of inhibitory GABAergic interneurons. Using cell‐attached recordings and single cell RT‐PCR, we have identified a subset of GABAergic interneurons in hippocampal region CA1 that express α1 adrenergic receptors (ARs). Application of the selective αAR agonist 6‐fluoronorepinephrine (6FNE) elicited an increase in action potential frequency in these cells (EC50 11μM). Pre‐treatment with 100nM of the α1 selective AR antagonist prazosin produced a significant rightward shift in the concentration response curve for 6FNE (EC50 221μM), an effect not seen when slices were pre‐treated with 100nM of the α2 selective AR antagonist rauwolscine (EC50 6.3μM), suggesting 6FNE is acting predominately through an α1 AR in these cells. RT‐PCR analysis of cytoplasm extracted from recorded cells revealed mRNA expression of the α1A AR, the α1B AR, or co‐expression of both receptors. Neuropeptide expression was also examined in the cytoplasmic samples and interestingly all 6FNE‐responsive interneurons were positive for somatostatin. Together, these results begin to define a cellular subset within the hippocampus that likely contributes to NE’s antiepileptic effect. Support: American Epilepsy Society, NSF CAREER 0347259, ND EPSCoR NSF EPS‐0447679 and NIH 5P20RR017699