Multiple Effects of Serotonin on Membrane Properties of Trigeminal Motoneurons In Vitro

Abstract

Intracellular recordings from guinea pig trigeminal motoneurons (TMNs) in brain stem slices were used to determine the underlying ionic mechanisms responsible for our previously demonstrated enhancement of TMN excitability during jaw movements by serotonin (5-HT). 5-HT (0.5-100 microM) depolarized motoneurons and increased input resistance in the majority of neurons tested. Additionally, 5-HT reduced the amplitude of the postspike medium-duration afterhyperpolarization, decreased the current threshold for maintained spike discharge, and increased the maximum slope of the steady-state spike frequency-current relationship. Under 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 inward 5-HT current (I(5-HT)) was linear throughout most of the voltage range tested. However, the steady-state I-V relationship showed some degree of inward rectification at potentials starting around -70 mV. The mean reversal potential for the instantaneous I(5-HT) was -86.2 +/- 4.5 (SE) mV (n = 9), a value slightly negative to the predicted potassium equilibrium potential of -82 mV in these neurons. In the presence of 2 mM Ba2+, 5-HT application did not produce a further reduction in input conductance, but did expose a Ba2+-insensitive residual inward current that was resistant to Cs+ application. The instantaneous I-V relationship 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 component of the total inward I(5-HT) was voltage independent and was blocked when the extracellular Na+ was replaced by choline, suggesting that the predominant charge carrier for this residual current is Na+. 5-HT enhanced a hyperpolarization-activated cationic current, I(h). In the presence of Ba2+, the time course of I(5-HT) resembled that of I(h) and showed a similar voltage dependence that was blocked by extracellular Cs+ (1-3 mM). The effects of 5-HT on membrane potential, input resistance, 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 excitability through modulation of multiple intrinsic membrane conductances. This provides for a mechanism(s) to fine tune the input-output discharge properties of these neurons, thus providing them with greater flexibility in output in response to time-varying synaptic inputs during various movements of the jaw.

Endogenous Serotonin Excites Striatal Cholinergic Interneurons via the Activation of 5-HT 2C, 5-HT6, and 5-HT7 Serotonin Receptors: Implications for Extrapyramidal Side Effects of Serotonin Reuptake Inhibitors

“…In particular, in agreement with our data on striatal cholinergic interneurons, in other neuronal populations the excitatory responses to 5-HT2C receptor activation have been reported to be mediated by the closing of K + channels (Hsiao et al, 1997;Xiang et al, 2005).…”

“…A closure of K leak channels was shown to mediate the 5-HTinduced depolarization in dorsal vagal neurons (Hopwood and Trapp, 2005) and to be involved in the response of trigeminal and spinal cord motoneurons to 5-HT (Hsiao et al, 1997;Kjaerulff and Kiehn, 2001). In caudal raphe and nucleus accumbens and in motoneurons of the spinal cord, 5-HT has been reported to reduce Kir conductance (North and Uchimura, 1989;Bayliss et al, 1997;Kjaerulff and Kiehn, 2001).…”

“…The residual Cs + -insensitive K + conductance might be carried by K leak channels. The identification of the additional cationic conductance activated by 5-HT needs further investigation (Hsiao et al, 1997).…”

The Whisking Rhythm Generator: A Novel Mammalian Network for the Generation of Movement

“…5-HT does not evoke rhythmic firing in guinea pig trigeminal motoneurons (Hsiao et al 1997). Thus whereas in other motor systems the actions of 5-HT on motoneurons is described as modulatory, capable of shaping an on-going rhythm but not responsible for the rhythm generation itself (Heckman et al 2004), in the vibrissa motor system, 5-HT is both necessary and sufficient for generating the whisking motor pattern and thus capable of generating rhythmic whisking.…”

Synaptic Release of Serotonin Induced by Stimulation of the Raphe Nucleus Promotes Plateau Potentials in Spinal Motoneurons of the Adult Turtle

“…In motoneurons, 5-HT induces multiple effects including depolarization (Larkman and Kelly, 1992;Hsiao et al, 1997;, inhibition of the medium AHP following action potentials (Berger et al, 1992;Hsiao et al, 1997;Grunnet et al, 2004), and facilitation of plateau potentials (Hounsgaard et al, 1988a;Hounsgaard and Kiehn, 1989;Bennett et al, 2001;Heckman et al, 2004). It was originally suggested that the facilitation of plateau potentials was a consequence of the inhibition of the AHP (Hounsgaard and Mintz, 1988;Schmidt and Jordan, 2000).…”