Presynaptic M1 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 CA1 pyramidal neurones revealed that CCh (1–3 μM)
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 concentration-dependent reduction of the amplitude of
the field excitatory postsynaptic potential (field EPSP) recorded
in the CA1 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 CA1 region and provide strong evidence that this effect
is mediated by muscarinic receptors of the M1 subtype.