title: Synaptically released 5-HT modulates the activity of tonically discharging neuronal populations in the rostral ventral medulla (RVM).
abstract: There is substantial evidence for an important modulating role of monoamines (catecholamines and serotonin, 5-HT) in the rostral ventral medulla (RVM), a region which plays an important role in cardiovascular and nociceptive functions. We investigated in slices the role of endogenous monoamines in the synaptic control of the activity of rat RVM neuronal populations using intracellular recordings in the lateral RVM plus lateral aspect of nucleus paragigantocellularis lateralis. A triple-labelling protocol allowed us to identify the location of impaled neurons and their eventual monoaminergic phenotype within the serotonergic and catecholaminergic populations of the RVM. Focal electrical stimulation revealed the existence of a functional monoaminergic input onto RVM neurons which was mediated by endogenous 5-HT acting at inhibitory 5-HT1A receptors but did not involve noradrenergic neurotransmission. The slow 5-HT-mediated inhibitory postsynaptic potential (IPSP) was only observed in the regularly discharging neurons, which were found to be neither catecholaminergic nor serotonergic. The synaptic release of 5-HT was, itself, under an inhibitory control involving GABAA (gamma-aminobutyric acid) receptors. Moreover, we characterized the effect of the 5-HT-releasing agent fenfluramine on this functional 5-HT-mediated synaptic transmission. Our results show that the effect of fenfluramine is biphasic consisting of an initial prolongation of the serotonergic IPSP followed by a decrease in amplitude. Our data provide a basis for the previously reported inhibitory effects of exogenously applied serotonin agonists/antagonists on the autonomic functions controlled by the RVM. This 5-HT pathway, which functionally links the serotonergic and catecholaminergic regions, might play an important role in cardiovascular and nociceptive functions.
authors.affiliation: Laboratoire de Neurophysiologie Cellulaire et Intégrée, UMR 7519 CNRS, 21, Rue René Descartes, 67084 Strasbourg cedex, France. piguet@neurochem.u-strasbg.fr
authors.forename: P
authors.initials: P
authors.lastname: Piguet
authors.forename: M E
authors.initials: ME
authors.lastname: Stoeckel
authors.forename: R
authors.initials: R
authors.lastname: Schlichter
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005277:Fenfluramine / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008526:Medulla Oblongata / Q000166:cytology / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009924:Organ Culture Techniques; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013331:Strychnine / Q000494:pharmacology; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D001640:Bicuculline; D018691:Excitatory Amino Acid Antagonists; D005277:Fenfluramine; D018756:GABA Antagonists; D018684:Glycine Agents; D007650:Ketanserin; D010879:Piperazines; D011224:Prazosin; D011433:Propranolol; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D013331:Strychnine; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine