ABSTRACT
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 (<10â¯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.
Subject(s)
Motor Neurons/metabolism , Serotonin/pharmacology , Tegmentum Mesencephali/metabolism , Action Potentials/physiology , Animals , Membrane Potentials/drug effects , Mesencephalon/metabolism , Motor Neurons/drug effects , Patch-Clamp Techniques , Rats , Rats, Sprague-Dawley , Receptors, Serotonin/metabolism , Serotonin/metabolism , Tegmentum Mesencephali/physiologyABSTRACT
Previous studies have indicated that the geniohyoid (GH) muscle receives innervation via both the hypoglossal nerve (CNXII) and the ansa cervicalis. Our recent studies revealed that the efferent root that contributes to the ansa cervicalis is a parasympathetic pathway and contains postganglionic cell bodies. Afferent axons from the GH muscle also travel via the ansa cervicalis, and afferent cell bodies are located in spinal ganglia. The present study attempts to locate the central terminations of these afferents. From the peripheral cut end of the ansa cervicalis, we recorded afferent discharges that coincided with inspiration and these were elicited by stretch of the GH muscle. After cutting CNXII proximal to its union with the ansa cervicalis, we applied horseradish peroxidase to the branch of CNXII that innervates the GH muscle. This procedure labeled cells ipsilaterally in the C2 spinal ganglia but not in the brainstem or upper spinal cord. Substance P-reactive terminals in the peripheral CNXII trunk were in apparent contact with vasoactive intestinal peptide-reactive cell bodies. Addition of the NK1 receptor agonist SP(NK1) excited parasympathetic postganglionic neurons and the specific NK1 receptor antagonist GR82334 blocked these effects in vitro. These results suggest that GH primary afferents synapse on parasympathetic postganglionic neurons in the CNXII trunk and that activation of SP(NK1) receptors modulates activity in these neurons.
Subject(s)
Afferent Pathways/physiology , Hypoglossal Nerve/physiology , Neurons, Afferent/physiology , Parasympathetic Fibers, Postganglionic/cytology , Receptors, Neurokinin-1/metabolism , Action Potentials/physiology , Animals , Dose-Response Relationship, Drug , Electromyography/methods , Hypoglossal Nerve/drug effects , Hypoglossal Nerve/metabolism , Immunohistochemistry/methods , In Vitro Techniques , Models, Biological , Neck Muscles/physiology , Neurokinin-1 Receptor Antagonists , Neurons, Afferent/drug effects , Peptide Fragments/pharmacology , Physalaemin/analogs & derivatives , Physalaemin/pharmacology , Rats , Rats, Wistar , Receptors, Neurokinin-1/agonists , Substance P/analogs & derivatives , Substance P/metabolism , Substance P/pharmacology , Vasoactive Intestinal Peptide/metabolism , Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate/metabolismABSTRACT
Trigeminal motoneurons are involved in a variety of oral motor activities, including mastication and breathing, which must be adapted to postnatal environmental change. Serotonin has both an excitatory and an inhibitory effect on trigeminal motor function, whereas substance P has mainly an excitatory effect. In the present study, we measured the density of serotonin- and substance P-immunoreactive nerve terminals in the trigeminal motor nucleus and the area 300 microm surrounding it in rats from embryonic day 19 to postnatal day 70. The density of these terminals gradually increased from embryonic day 19 to postnatal day 7 and decreased thereafter. The density was greatest in the ventromedial subnucleus of the trigeminal motor nucleus at embryonic day 19 and postnatal day 0 and in the area 300 microm surrounding trigeminal motor nucleus at postnatal day 4 and older. Two-color fluorescence immunohistochemistry was used to identify nerve processes immunoreactive for both substance P and serotonin. Approximately, 90% of serotonergic terminals also contained substance P at all ages examined, which suggests that the physiological function of terminals in which these neurotransmitters are colocalized is similar throughout development.
