Excitatory effects of serotonin on rat striatal cholinergic interneurones

We investigated the effects of 5-hydroxytryptamine (5-HT, serotonin) in striatal cholinergic interneurones with gramicidin-perforated whole-cell patch recordings. Bath-application of serotonin (30 mu M) significantly and reversibly increased the spontaneous firing rate of 37/45 cholinergic interneurones tested. On average, in the presence of serotonin, firing rate was 273 +/- 193% of control. Selective agonists of 5-HT1A, 5-HT3, 5-HT4 and 5-HT7 receptors did not affect cholinergic interneurone firing, while the 5-HT2 receptor agonist alpha-methyl-5-HT (30 mu M) mimicked the excitatory effects of serotonin. Consistently, the 5-HT2 receptor antagonist ketanserin (10 mu M) fully blocked the excitatory effects of serotonin. Two prominent after-hyperpolarizations (AHPs), one of medium duration that was apamin-sensitive and followed individual spikes, and one that was slower and followed trains of spikes, were both strongly and reversibly reduced by serotonin; these effects were fully blocked by ketanserin. Conversely, the depolarizing sags observed during negative current injections and mediated by hyperpolarization-activated cationic currents were not affected. In the presence of apamin and tetrodotoxin, the slow AHP was strongly reduced by 5-HT, and fully abolished by the calcium channel blocker nickel. These results show that 5-HT exerts a powerful excitatory control on cholinergic interneurones via 5-HT2 receptors, by suppressing the AHPs associated with two distinct calcium-activated potassium currents.