Regulation of muscarinic acetylcholine receptor-mediated synaptic responses by GABA(B) receptors in the rat hippocampus

1. Both GABAB and muscarinic, acetylcholine receptors (mAChRs) influence hi ppocampal-dependent mnemonic processing, Here the possibility of a direct i nteraction between GABAB receptors and mAChR-mediated synaptic responses ha s been studied using intracellular recording in rat hippocampal slices. 2. The GABA(B) receptor agonist (-)-baclofen (5-10 mum) depressed an atropi ne-sensitive slow EPSP(EPSPM) and occluded the GABA(B)-receptor-mediated IP SP (IPSPB) which preceded it, These inhibitory effects were accompanied by postsynaptic hyperpolarization (9 +/- 2 mV) and a reduction in cell input r esistance (12 +/- 3 %). 3. The selective GABA(B) receptor antagonist CGP 55845A (1 muM) fully rever sed the depressant effects of (-)-baclofen (5-10 mum) such that in the comb ined presence of (-)-baclofen and CGP 55845A the EPSPM, was 134 +/- 21 % of control. 4. (-)-Baclofen (5-10 mum) caused a small (28 +/- 11 %) inhibition of carba chol-induced (3.0 mum) postsynaptic depolarizations and increases in input resistance. 5. CGP 55845A (1 mum) alone caused an increase in the amplitude of the EPSP M (253 +/- 74 % of control) and blocked the IPSPB that preceded it. 6. In contrast, the selective GABA uptake inhibitor NNC 05-0711 (10 mum) in creased the amplitude of the IPSPB by 141 +/- 38 % and depressed the amplit ude of the EPSPM by 58 +/- 10 %. This inhibition was abolished by CGP 55845 A (1 mum). 7. Taken together these data provide good evidence that synaptically releas ed GABA activates GABA(B) receptors that inhibit mAChR-mediated EPSPs in hi ppocampal CA1 pyramidal neurones. The mechanism of inhibition may involve b oth pre- and postsynaptic elements.