Abstract
In the presence of spiperone to block the 5‐HT~1A~‐mediated inhibition of pyramidal cell activity, 5‐hydroxytryptamine (serotonin, 5‐HT) produces a rapid transient increase in amplitude of the extracellularly recorded population spike from area CA1 of the hippocampus. Intracellular recording techniques in area CA1 of rat hippcampal slices were used to identify the ionic mechanism and to characterize the 5‐HT receptor mediating this excitatory response to 5‐HT. Most of the experiments were conducted in the presence of spiperone to block the 5HT~1A~ hyperpolarization. Since spiperone also has high affinity for 5‐HT~2~ receptors, any response mediated by 5‐HT~2~ receptors would also be blocked. Bath perfusion of the slice with 5‐HT increased the rectification of pyramidal cells in the subthreshold region, increased the resistance, and increased the amplitude of subthreshold excitatry postsynaptic potentials (EPSPs) to initiate spike firing. The 5‐HT~2,1C~‐selective agonist DOI mimicked this effect of 5‐HT, and the 5‐HT~2,1C~ antagonist ketanserin (1 μM) blocked the effect of DOI. There was no change in the amplitude of the slow afterhyperpolarization (IPSPs). The increase in rectification and EPSP amplitude by 5‐HT occurred even in the presence of the 5‐HT~4~‐selective antagonist BRL 24924 to prevent the decrease in amplitude of the sAHP by 5‐HT. We conclude that 5‐HT produces a fast excitatory response by increasing subthreshold conductance in CA1 hippocampal pyramidal cells. The identity of the receptor mediating this response was not conclusively identified, but resembled the 5‐HT~1C~ receptor.