Postsynaptic GABAB receptors enhance extrasynaptic GABAA receptor function in dentate gyrus granule cells

Abstract

Ambient GABA in the brain tonically activates extrasynaptic GABAA receptors, and activity-dependent changes in ambient GABA concentration can also activate GABAB receptors. To investigate an interaction between postsynaptic GABAB and GABAA receptors, we recorded GABAA currents elicited by exogenous GABA (10 μM) from dentate gyrus granule cells (DGGCs) in adult rat hippocampal slices. The GABAB receptor agonist baclofen (20 μM) enhanced GABAA currents. This enhancement was blocked by the GABAB receptor antagonist CGP 55845 and intracellular solutions containing the GTP analog GDP-β-s, indicating that baclofen was acting on postsynaptic GABAB receptors. Modulation of GABAA currents by postsynaptic GABAB receptors was not observed in CA1 pyramidal cells or layer 2/3 cortical pyramidal neurons. Baclofen reduced the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) but did not alter sIPSC amplitude or kinetics. Thus, GABAA receptors activated at synapses were not modulated by postsynaptic GABAB receptors. In contrast, tonic GABA currents and currents activated by the GABAA receptor δ subunit-selective agonist THIP (10 μM) were potentiated by baclofen. Our data indicate that postsynaptic GABAB receptors enhance the function of extrasynaptic GABAA receptors, including δ subunit-containing receptors that mediate tonic inhibition in DGGCs. The modulation of GABAA receptor function by postsynaptic GABAB receptors is a newly identified mechanism that will influence the inhibitory tone of DGGCs when GABAB and GABAA receptors are both activated. © 2013 the authors.