Selective inhibition of local excitatory synaptic transmission by serotonin through an unconventional receptor in the CA1 region of rat hippocampus

1. The modulation of synaptic transmission by serotonin (5-HT) was studied using whole-cell voltage-clamp and sharp-electrode current-clamp recordings from CA1 pyramidal neurones in transverse rat hippocampal slices in vitro. 2. With GABA(A) receptors blocked, polysynaptic transmission evoked by stra tum radiatum stimulation was inhibited by submicromolar concentrations of 5 -HT, while monosynaptic excitatory transmission and CA1 pyramidal neurone e xcitability were unaffected. The effect persisted following pharmacological blockade of 5-HT1A and 5-HT4 receptors, which directly affect CA1 pyramida l neurone excitability. 3. Concentration-response relationships for 5-HT were determined in individ ual neurones; the EC50 values for block of polysynaptic excitation and inhi bition by 5-HT were similar to 230 and similar to 160 nar, respectively. Th e 5-HT receptor type responsible for the observed effect does not fall easi ly into the present classification of 5-HT receptors. 4. 5-HT inhibition of polysynaptic EPSCs persisted following complete block of GABAergic transmission and in CA1 minislices, ruling out indirect effec ts through interneurones and non CA1. pyramidal neurones, respectively. 5. Monosynaptic EPSCs evoked by stimulation of CA1 afferent pathways appear ed to be unaffected by 5-HT. Monosynaptic EPSCs evoked by stimulation of th e alveus, which contains CA1 pyramidal neurone axons, were partially inhibi ted by 5-HT. 6. We conclude that 5-HT inhibited synaptic transmission by acting at local recurrent collaterals of CA1 pyramidal neurones. This may represent an imp ortant physiological action of 5-HT in the hippocampus, since it occurs ove r a lower concentration range than the 5-HT effects reported so far.