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 (I_h), as the basis of this property, regulates the spike discharge characteristics and input frequency preference (resonance) in these neurons, suggesting that I_h modulation is an important regulator of oral motor activity. To examine a possible contribution of serotonin (5-HT) to the modulation of I_h activation characteristics, in the present study, we investigated the modulatory effects of 5-HT receptor activation on I_h in postnatal day (P) 2-12 rat Mes V neurons by whole-cell patch-clamp recording. Bath application of 5-HT suppressed the I_h-dependent voltage sag and I_h conductance, but induced only a modest shift in the voltage dependence of I_h activation. This 5-HT-induced suppression of I_h 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-HT_1A receptor mimicked the effect of 5-HT, while modulation of other receptor subtypes, including 5-HT_1B,1D, 5-HT₂, and 5-HT₃, had little or no effect on I_h. Low-frequency (<10 Hz) resonance at membrane potentials below the resting potential were reduced by 5-HT, suggesting that serotonergic I_h modulation can substantially alter the frequency preference to synaptic inputs. These results suggest that changes in resonance properties through serotonergic modulation of I_h 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.