MULTIPLE EFFECTS OF SEROTONIN ON MEMBRANE-PROPERTIES OF TRIGEMINAL MOTONEURONS IN-VITRO

Intracellular recordings from guinea pig trigeminal motoneurons (TMNs) in brain stem slices were used to determine the underlying ionic mech anisms responsible for our previously demonstrated enhancement of TMN excitability during jaw movements by serotonin (5-HT). 5-HT (0.5-100 m u M) depolarized motoneurons and increased input resistance in the maj ority of neurons tested. Additionally, 5-HT reduced the amplitude of t he postspike medium-duration afterhyperpolarization, decreased the cur rent threshold for maintained spike discharge, and increased the maxim um slope of the steady-state spike frequency-current relationship. Und er voltage clamp, from holding potentials close to resting potential, 5-HT produced an inward current and a decrease in instantaneous slope conductance, suggesting a reduction In a resting K+ leak conductance ( I-leak). The instantaneous current-voltage(I-V) relationship for the i nward 5-HT current (I5-HT) was linear throughout most of the voltage r ange tested. However, the steady-state I-V relationship showed some de gree of inward rectification at potentials starting around -70 mV. The mean reversal potential for the instantaneous 1(5-HT) was -86.2 +/- 4 .5 (SE) mV (n = 9), a value slightly negative to the predicted potassi um equilibrium potential of -82 mV in these neurons. In the presence o f 2 mM Ba2+, 5-HT application did nor produce a further reduction in i nput conductance, but did expose a Ba2+-insensitive residual inward cu rrent that was resistant to Cs+ application. The instantaneous I-V rel ationship during 5-HT application in the presence of Ba2+ was shifted downward and parallel to control, suggesting that Ba2+ and 5-HT block the same resting I-leak. The residual Ba2+- and Cs+-insensitive compon ent of the total inward I5-HT was voltage independent and was blocked when the extracellular Na+ was replaced by choline, suggesting that th e predominant charge carrier for this residual current is Na+. 5-HT en hanced a hyperpolarization-activated cationic current, I-h. In the pre sence of Ba2+, the time course of 1(5-HT) resembled that of I-h and sh owed a similar voltage dependence that was blocked by extracellular Cs + (1-3 mM). The effects of 5-HT on membrane potential, input resistanc e, and I-h were partially mimicked by 5-HT2 agonists and suppressed by 5-HT2 antagonists. It is concluded that 5-HT enhances TMN membrane ex citability through modulation of multiple intrinsic membrane conductan ces. This provides for a mechanism(s) to fine tune the input-output di scharge properties of these neurons, thus providing them with greater flexibility in output in response to time-varying synaptic inputs duri ng various movements of the jaw.