Regulation of muscarinic acetylcholine receptor-mediated synaptic responses by GABA(B) receptors in the rat hippocampus.
1. Both GABA(B) and muscarinic acetylcholine receptors (mAChRs) influence hippocampal-dependent mnemonic processing. Here the possibility of a direct interaction between GABA(B) receptors and mAChR-mediated synaptic responses has been studied using intracellular recording in rat hippocampal slices. 2. The GABA(B) receptor agonist (-)-baclofen (5-10 microM) depressed an atropine-sensitive slow EPSP (EPSP(M)) and occluded the GABA(B)-receptor-mediated IPSP (IPSP(B)) 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 GABA(B) receptor antagonist CGP 55845A (1 microM) fully reversed the depressant effects of (-)-baclofen (5-10 microM) such that in the combined presence of (-)-baclofen and CGP 55845A the EPSP(M) was 134 +/- 21 % of control. 4. (-)-Baclofen (5-10 microM) caused a small (28 +/- 11 %) inhibition of carbachol-induced (3.0 microM) postsynaptic depolarizations and increases in input resistance. 5. CGP 55845A (1 microM) alone caused an increase in the amplitude of the EPSP(M) (253 +/- 74 % of control) and blocked the IPSP(B) that preceded it. 6. In contrast, the selective GABA uptake inhibitor NNC 05-0711 (10 microM) increased the amplitude of the IPSP(B) by 141 +/- 38 % and depressed the amplitude of the EPSP(M) by 58 +/- 10 %. This inhibition was abolished by CGP 55845A (1 microM). 7. Taken together these data provide good evidence that synaptically released GABA activates GABA(B) receptors that inhibit mAChR-mediated EPSPs in hippocampal CA1 pyramidal neurones. The mechanism of inhibition may involve both pre- and postsynaptic elements.
Morton
R A
RA
MRC Centre for Synaptic Plasticity, University of Bristol, University Walk, Bristol BS8 1TD, UK.
Manuel
N A
NA
Bulters
D O
DO
Cobb
S R
SR
Davies
C H
CH
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001418:Baclofen / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010721:Phosphinic Acids / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D018755:GABA Agonists; D018756:GABA Antagonists; D018727:Muscarinic Antagonists; D010721:Phosphinic Acids; D011412:Propanolamines; D018080:Receptors, GABA-B; D011976:Receptors, Muscarinic; C085075:CGP 55845A; D005680:gamma-Aminobutyric Acid; D001285:Atropine; D001418:Baclofen