Serotonin suppresses subthreshold and suprathreshold oscillatory activity of rat inferior olivary neurones in vitro

1. The effect of serotonin on membrane potential oscillations of inferior olivary neurones was studied in brainstem slices from 10- to 19-day-old rats. 2. Serotonin at 50 and 5 mu M induced a mean depolarization of 9.4 and 7.7 mV, respectively, that was preceded by a reversible suppression of subthreshold membrane potential oscillations. These effects were not changed by 1 mu M tetrodotoxin and the suppression of subthreshold oscillations persisted after current-mediated restoration of resting potential. 3. In spontaneously active neurones, serotonin abolished thr:rhythmicity of action potential firing without; affecting spike frequency. 4. Serotonin reduced the slope of the calcium-mediated rebound spike and both the duration and amplitude of the subsequent after hyperpolarization. Serotonin also shifted the voltage dependence of the rebound spike to more negative values. 5. Hyperpolarizing current; pulses (200 ms) revealed that serotonin increased the pre-rectification and steady-et;ate components of membrane resistance by 37 and 38%, respectively, in 66% of neurones, but decreased these parameters by 14 and 20 % in the remaining cells. 6. The serotonin effects were antagonized by 5 mu M methysergide or 1-5 mu M ketanserin and were mimicked by 10-20 mu M dimethoxy-4-iodoamphetamine but not 10 mu M 8-hydroxy-2-(di-N-propylamino)-tetralin. 7. The data indicate that serotonin suppresses the rhythmic activity of olivary neurones via 5-HT(2) receptors by inhibition of the T-type calcium current in combination with membrane depolarization due to activation of a cation current (I(h)) and block of a resting K(+) current (fast I(K(ir))). This modulatory action of serotonin may account fur the differential propensity of olivary neurones to fire rhythmically during different behavioural states in vivo.