The subiculum is the major output region of the hippocampal network. It receives inputs from CA1 and entorhinal cortex regions and sends projections to several cortical and subcortical areas. The subiculum is involved in cognitive tasks including spatial orientation or novel object recognition memory. Under pathological conditions, the subiculum is responsible for certain forms of temporal lobe epilepsy. In this study, we investigated how serotonin (5-HT) modulates the activity of principal cells from the subiculum at the subcellular level.We recorded the electrical activity of subicular pyramidal neurons with the whole-cell patch clamp technique in a slice preparation from the hippocampus of mice (P7 to P36). In agreement with previous observations, we found that subicular neurons fired action potentials in bursts caused by the presence of a low threshold spike generated by T-type Ca2+ channels. A glass pipette filled with 5-HT was positioned near the membrane of the recorded cell and released either by pressure or microiontophoresis. A local puff of 5-HT inhibited the generation of action potentials. During voltage-clamp recordings performed after blocking currents mediated by Na+ and K+ currents, puffing 5-HT decreased the amplitude of a low-threshold voltage sensitive transient inward current sensitive to mibefradil. These results suggest that 5-HT inhibits a current mediated by T-type Ca2+ channels. To corroborate our findings, we monitored the variations in calcium concentrations by loading recorded cells with the calcium indicator FURA-2. We observed that a burst firing evoked by depolarizing current pulses induced an increase in calcium concentration. When 5-HT was puff-applied, the calcium signal was attenuated in all compartments of the neuron (AIS, soma, dendrites). Puffing the 5-HT2C agonist WAY 629 instead of 5-HT had the same inhibitory effect on firing and Ca2+ current.Our data suggest that 5-HT modulates the activity of subicular pyramidal cells by inhibiting T-type calcium channels through an activation of 5-HT2C receptors. We suggest that the pathway we uncovered prevent the development of epileptic seizures for healthy subjects.