| 5-hydroxytryptamine (serotonin,5-HT), an indolamine widely distributed in the peripheral tissues and the central nervous system, is involved in a large variety of physiological functions and pathogenesis including pain modulation, sleep, endocrine, cardiopulmonary function and psychiatric disorders such as depression, anxiety and aggressiveness. Anatomical studies have found that5-HT containing neurons are mainly within the raphe nuclei (pallidus, obscurus, magnus). Serotonergic neurons project to the whole brain and synapse upon many kind of neurons.In recent years, many in vivo electrophysiological studies have shown that5-HT plays an important role in the genesis of respiratory rhythm and in the control of respiratory motoneurons, which involves many receptor subtypes including5-HT1A,5-HT2,5-HT4,5-HT7. Disfunction of serotonergic mechanism is related to many kinds of respiratory diseases. In the pre-B□tzinger complex (PBC) in the medulla, where the breathing rhythm is generated by a neuronal network,5-HT plays an important role in mediating the generation of respiratory rhythm and patterns. Serotonin receptors are widely distributed in respiratory motoneurons (such as hypoglossal motoneurons, phrenic motoneurons and laryngeal motoneurons). At least in animals, works from some laboratories have shown that a central5-HT pathway is involved in the reflex activation of tracheobronchial preganglionic vagal motoneurons (TPVM). Activation of central5-HT1A receptors causes an increase in the vagal tone to the airway producing bronchoconstriction. Furthermore, reflex activation of these tracheobronchial preganglionic vagal motoneurones by the stimulation of bronchial and pulmonary C-fibre’irritant’receptors can be attenuated by central administration of5-HT1A receptor antagonists and potentiated by5-HT uptake inhibitor, indicating that5-HT1A receptors play an important role in the regulation of tracheobronchial preganglionic vagal motoneurons.Previous studies have made much progress about the central distribution and the synaptic control of tracheobronchial preganglionic vagal motoneurons (TPVM). Tracer application directly to the tracheal wall labeled the putative TPVMs both in the compact portion of the nucleus ambiguous (can) and in the area ventro/ventrolateral to cNA(vNA), and TPVMs were found to receive both excitatory and inhibitory synaptic inputs. However, regarding the5-HT modulation of TPVMs nothing has been known at synaptic level. In this study TPVMs were retrogradely labeled by injecting rhodamine into the tracheal wall and were identified by the presence of fluorescence in brainstem slices, and the effects of5-HTiA/7agonists on the synaptic inputs of TPVMs were examined using whole-cell patch-clamp technique.Following are the results and conclusions:1.5-HT1A/7receptor agonist8-OH-DPAT significantly inhibited the frequency and amplitude of the GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) of TPVMs, which could be blocked by5-HT1A/7receptor antagonist WAY100635. Whereas8-OH-DPAT had no effect on the GABAergic miniature inhibitory postsynaptic currents (mIPSCs) of TPVMs. These findings suggested that5-HT1A/7receptor agonist might indirectly excite TPVMs through inhibition of their GABAergic inputs.2.8-OH-DPAT significantly inhibited the frequency and amplitude of the glycinergic spontaneous inhibitory postsynaptic currents (sIPSCs) of TPVMs, which could be blocked by5-HT1A/7receptor antagonist WAY100635. Whereas8-OH-DPAT had no effect on the glycinergic miniature inhibitory postsynaptic currents (mlPSCs) of TPVMs. These findings suggested that5-HT1A/7receptor agonist might indirectly excite TPVMs through inhibition of their glycinergic inputs.3.8-OH-DPAT had no effect on the glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs).These results at least in part revealed the synaptic mechanisms involved in the activation of tracheobronchial preganglionic vagal motoneurons (TPVM) by central5-HT. |
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