Partial hippocampal kindling increases GABA B receptor-mediated postsynaptic currents in CA1 pyramidal cells

Abstract

In previous studies, we showed that partial hippocampal kindling decreased the efficacy of the presynaptic GABA B receptors on both GABAergic and glutamatergic terminals of CA1 neurons in hippocampal slices in vitro. In this study, GABA B receptor-mediated inhibitory postsynaptic currents (GABA B-IPSCs) were assessed by whole-cell recordings in CA1 pyramidal neurons in hippocampal slices of male Long–Evans rats. The peak GABA B-IPSC evoked by a brief train of supramaximal stratum radiatum stimuli (20 pulses of 300 Hz) in the presence of picrotoxin (0.1 mM) and kynurenic acid (1 mM) was larger in neurons of kindled (65.9±5.2 pA, N=42 cells) than control (45.8±4.8 pA, N=32 cells) rats ( P<0.01). Adding GABA uptake blocker nipecotic acid (1 mM) or GABA B receptor agonist baclofen (0.01 mM) in the perfusate induced outward currents that were blocked by GABA B receptor antagonist CGP 55845A (1 μM). The peak outward current induced by nipecotic acid was larger in neurons of the kindled (55.4±5.7 pA, N=30) than the control group (39.8±4.5 pA, N=28) ( P<0.05). However, the magnitude of the baclofen-induced current was not different between kindled (90.8±6.9 pA, N=29) and control (87.2±5.9 pA, N=21) groups ( P>0.05). We concluded that partial hippocampal kindling increased GABA B-IPSCs in hippocampal CA1 pyramidal cells via multiple presynaptic mechanisms.