RT Journal Article SR Electronic T1 Long-lasting potentiation and epileptiform activity produced by GABAB receptor activation in the dentate gyrus of rat hippocampal slice JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 1198 OP 1209 DO 10.1523/JNEUROSCI.11-05-01198.1991 VO 11 IS 5 A1 EC Burgard A1 JM Sarvey YR 1991 UL http://www.jneurosci.org/content/11/5/1198.abstract AB Bath application of the GABAB receptor agonist baclofen produced a concentration-dependent long-lasting potentiation (LLP) of the evoked population spike in the dentate gyrus of rat hippocampal slices. A high concentration of baclofen (5 microM) also produced a loss of inhibition that was manifested as the appearance of epileptiform, multiple evoked population spikes and a decrease in paired-pulse inhibition. Both baclofen-induced potentiation and epileptiform activity could be blocked or significantly reduced in slices from pertussis toxin-treated animals (1 microgram, intradentate) or in slices pretreated with the NMDA receptor antagonist D-(-)-2-amino-5-phosphonovaleric acid (10 microM). At a concentration that had no significant effect on individual evoked responses (0.1 microM) but still produced a loss in paired-pulse inhibition, baclofen facilitated the induction of beta- adrenergic receptor-mediated LLP. LLP was induced in the dentate gyrus by bath application of 1 microM, but not 0.1 microM, isoproterenol. Coapplication of baclofen and isoproterenol, both at a concentration (0.1 microM) that individually had no effect on the population spike, produced a synergistic LLP of the population spike. We propose that baclofen produces a selective disinhibitory effect in the granule cell layer of the dentate gyrus by inhibiting the activity of GABAergic interneurons. At a low concentration, the subtle loss of inhibition can facilitate the induction of isoproterenol-induced LLP. At a high concentration, baclofen can produce an LLP that is probably induced by a loss of inhibition.