Regulation of muscarinic acetylcholine receptor‐mediated synaptic responses by GABAB receptors in the rat hippocampus

1 Both GABAB and muscarinic acetylcholine receptors (mAChRs) influence hippocampal‐dependent mnemonic processing. Here the possibility of a direct interaction between GABAB receptors and mAChR‐mediated synaptic responses has been studied using intracellular recording in rat hippocampal slices. 2 The GABAB receptor agonist (‐)‐baclofen (5‐10 μm) depressed an atropine‐sensitive slow EPSP (EPSPM) and occluded the GABAB‐receptor‐mediated IPSP (IPSPB) which preceded it. These inhibitory effects were accompanied by postsynaptic hyperpolarization (9 ± 2 mV) and a reduction in cell input resistance (12 ± 3 %). 3 The selective GABAB receptor antagonist CGP 55845A (1 μm) fully reversed the depressant effects of (−)−baclofen (5‐10 μm) such that in the combined presence of (−)−baclofen and CGP 55845A the EPSPM was 134 ± 21 % of control. 4 (−)−Baclofen (5–10 μm) caused a small (28 ± 11 %) inhibition of carbachol‐induced (3.0 μm) postsynaptic depolarizations and increases in input resistance. 5 CGP 55845A (1 μm) alone caused an increase in the amplitude of the EPSPM (253 ± 74 % of control) and blocked the IPSPB that preceded it. 6 In contrast, the selective GABA uptake inhibitor NNC 05‐0711 (10 μm) increased the amplitude of the IPSPB by 141 ± 38 % and depressed the amplitude of the EPSPM by 58 ± 10 %. This inhibition was abolished by CGP 55845A (1 μm). 7 Taken together these data provide good evidence that synaptically released GABA activates GABAB receptors that inhibit mAChR‐mediated EPSPs in hippocampal CA1 pyramidal neurones. The mechanism of inhibition may involve both pre− and postsynaptic elements.