M 1 muscarinic cholinoceptors mediate inhibition of excitatory synaptic transmission in the hippocampus in vitro

The effects of the cholinoceptor agonist, carbachol (CCh), were examined in the rat hippocampal slice preparation. Intracellular recordings from CA 1 pyramidal neurones revealed that CCh (1-3/~M) inhibited excitatory postsynaptic responses evoked by stimulation of the Schaffer collateral/commissural pathway while, at the same time, direct excitability was enhanced. Extracellularly, CCh produced a concentrationdependent reduction of the amplitude of the field excitatory postsynaptic potential (field EPSP) recorded in the CAI apical dendritic region. The muscarinic receptor antagonist, pirenzepine, competitively antagonized the effects of CCh on the field EPSP with a pA2 of 7.4. These results confirm earlier reports of a presynaptic inhibitory action of CCh in the hippocampal CAI region and provide strong evidence that this effect is mediated by muscarinic receptors of the Mt subtype.