Serotonin enhances excitability in neostriatal neurons by reducing voltage-dependent potassium currents

The physiological effects of serotonin (5-HT) on rat neostriatal neurons were investigated using current-clamp techniques in neostriatal slices and voltage-clamp techniques in acutely dissociated adult neostriatal neurons. In most neurons (35/51), bath-applied 5-HT (10-60 microM) decreased the first spike latency and increased the evoked firing frequency. Membrane input resistance was also increased in most neurons (33/35) but could not explain the enhanced responsiveness. Tetrodotoxin, at concentrations sufficient to block spike production, did not block the ability of 5-HT to enhance the slow ramp-like voltage trajectory produced by depolarizing current injection. The role of potassium currents in the 5-HT effect was examined using whole cell voltage-clamp; in 6 of 9 neurons, 5-HT reversibly decreased inactivating potassium currents activated by depolarization. These experiments suggest that 5-HT's effect on the ramp trajectory may be mediated by a reduction of potassium currents activated by sub-threshold depolarization.