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 o livary 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 subthres hold membrane potential oscillations. These effects were not changed by 1 m u 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 bo th the duration and amplitude of the subsequent after hyperpolarization. Se rotonin also shifted the voltage dependence of the rebound spike to more ne gative values. 5. Hyperpolarizing current; pulses (200 ms) revealed that serotonin increas ed the pre-rectification and steady-et;ate components of membrane resistanc e by 37 and 38%, respectively, in 66% of neurones, but decreased these para meters 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 bu t not 10 mu M 8-hydroxy-2-(di-N-propylamino)-tetralin. 7. The data indicate that serotonin suppresses the rhythmic activity of oli vary neurones via 5-HT2 receptors by inhibition of the T-type calcium curre nt in combination with membrane depolarization due to activation of a catio n current (I-h) and block of a resting K+ current (fast I-K(ir)). This modu latory action of serotonin may account fur the differential propensity of o livary neurones to fire rhythmically during different behavioural states in vivo.