Serotonergic modulation of slow inward rectification in mesencephalic trigeminal neurons.

Inward rectification in response to membrane hyperpolarization is a prominent feature of mesencephalic trigeminal (Mes V) neurons and the hyperpolarization-activated inward current (Ih), as the basis of this property, regulates the spike discharge characteristics and input frequency preference (resonance) in these neurons, suggesting that Ih modulation is an important regulator of oral motor activity. To examine a possible contribution of serotonin (5-HT) to the modulation of Ih activation characteristics, in the present study, we investigated the modulatory effects of 5-HT receptor activation on Ih in postnatal day (P) 2-12 rat Mes V neurons by whole-cell patch-clamp recording. Bath application of 5-HT suppressed the Ih-dependent voltage sag and Ih conductance, but induced only a modest shift in the voltage dependence of Ih activation. This 5-HT-induced suppression of Ih was greater in P10-12 than P2-4 neurons, and involved the cAMP/protein kinase A (PKA) signaling pathway but not the PKC pathway. Pharmacological activation of the 5-HT1A receptor mimicked the effect of 5-HT, while modulation of other receptor subtypes, including 5-HT1B,1D, 5-HT2, and 5-HT3, had little or no effect on Ih. Low-frequency (<10 Hz) resonance at membrane potentials below the resting potential were reduced by 5-HT, suggesting that serotonergic Ih modulation can substantially alter the frequency preference to synaptic inputs. These results suggest that changes in resonance properties through serotonergic modulation of Ih may tune the firing of Mes V neurons to different afferent input frequencies and alter motor outputs to the jaw, thereby regulating oral motor activity.