title: Serotonin activates catecholamine neurons in the solitary tract nucleus by increasing spontaneous glutamate inputs.
abstract: Serotonin (5-HT) is a critical neurotransmitter in the control of autonomic functions. 5-HT(3) receptors participate in vagal afferent feedback to decrease food intake and regulate cardiovascular reflexes; however, the phenotype of the solitary tract nucleus (NTS) neurons involved is not known. A(2)/C(2) catecholamine (CA) neurons in the NTS are directly activated by visceral afferents and are important for the control of food intake and cardiovascular function, making them good candidates to respond to and mediate the effects of serotonin at the level of the NTS. This study examines serotonin's effects on NTS-CA neurons using patch-clamp techniques and transgenic mice expressing an enhanced green fluorescent protein driven by the tyrosine hydroxylase (TH) promoter (TH-EGFP) to identify catecholamine neurons. Serotonin increased the frequency of spontaneous glutamate excitatory postsynaptic currents (sEPSCs) in >90% of NTS-TH-EGFP neurons, an effect blocked by the 5-HT(3) receptor antagonist ondansetron and mimicked by the 5-HT(3) receptor agonists SR5227 and mCPBG. In contrast, 5-HT(3) receptor agonists increased sEPSCs on a minority (<30%) of non-TH neurons. 5-HT(3) receptor agonists increased the frequency, but not the amplitude, of mini-EPSCs, suggesting that their actions are presynaptic. 5-HT(3) receptor agonists increased the firing rate of TH-EGFP neurons, an effect dependent on the increased spontaneous glutamate inputs as it was blocked by the ionotropic glutamate antagonist NBQX, but independent of visceral afferent activation. These results demonstrate a cellular mechanism by which serotonin activates NTS-TH neurons and suggest a pathway by which it can increase catecholamine release in target regions to modulate food intake, motivation, stress, and cardiovascular function.
authors.affiliation: Program in Neuroscience, Department of Veterinary Comparative Anatomy, Physiology and Pharmacology, Washington State University, Pullman, Washington 99164, USA.
authors.forename: Ran Ji
authors.initials: RJ
authors.lastname: Cui
authors.forename: Brandon L
authors.initials: BL
authors.lastname: Roberts
authors.forename: Huan
authors.initials: H
authors.lastname: Zhao
authors.forename: Mingyan
authors.initials: M
authors.lastname: Zhu
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Appleyard
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002395:Catecholamines / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D018698:Glutamic Acid / Q000502:physiology*; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D017661:Receptors, Presynaptic / Q000187:drug effects; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017552:Solitary Nucleus / Q000166:cytology / Q000187:drug effects*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
chemical_list: D002395:Catecholamines; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D011719:Pyrazines; D011810:Quinoxalines; D017661:Receptors, Presynaptic; D044406:Receptors, Serotonin, 5-HT3; D017366:Serotonin Receptor Agonists; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D012701:Serotonin; D018698:Glutamic Acid; C014896:6-chloro-2-(1-piperazinyl)pyrazine; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D014446:Tyrosine 3-Monooxygenase