title: Presynaptic serotonergic gating of the subthalamonigral glutamatergic projection.
abstract: The GABAergic projection neurons in the substantia nigra pars reticulata (SNr) are key basal ganglia output neurons. The activity of these neurons is critically influenced by the glutamatergic projection from the subthalamic nucleus (STN). The SNr also receives an intense serotonin (5-HT) innervation, raising the possibility that 5-HT may regulate the STN→SNr glutamatergic transmission and the consequent STN-triggered spike firing in SNr neurons. Here we show that 5-HT reduced STN stimulation-evoked long-lasting polysynaptic complex EPSCs in SNr GABA neurons. This inhibitory 5-HT effect was mimicked by the 5-HT1B receptor agonist CP93129 and blocked by the 5-HT1B antagonist NAS-181. 5-HT1A receptor ligands were ineffective. Additionally, 5-HT and CP93129 reduced the frequency but not the amplitude of miniature EPSCs, suggesting a reduced vesicular release. 5-HT and CP93129 also decreased the amplitude but increased the paired pulse ratio of the monosynaptic EPSCs in SNr GABA neurons, indicating a presynaptic 5-HT1B receptor-mediated inhibition of glutamate release. Furthermore, 5-HT and CP93129 inhibited STN-triggered burst firing in SNr GABA neurons, and CP93129's inhibitory effect was strongest when puffed to STN→SNr axon terminals in SNr, indicating a primary role of the 5-HT1B receptors in these axon terminals. Finally, the 5-HT1B receptor antagonist NAS-181 increased the STN-triggered complex EPSCs and burst firing in SNr GABA neurons, demonstrating the effects of endogenous 5-HT. These results suggest that nigral 5-HT, via presynaptic 5-HT1B receptor activation, gates the excitatory STN→SNr projection, reduces burst firing in SNr GABA neurons, and thus may play a critical role in movement control.
authors.affiliation: Department of Pharmacology, University of Tennessee College of Medicine, Memphis, Tennessee 38163, USA.
authors.forename: Shengyuan
authors.initials: S
authors.lastname: Ding
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Fu-Ming
authors.initials: FM
authors.lastname: Zhou
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D059330:GABAergic Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D005971:Glutamates / Q000378:metabolism*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013378:Substantia Nigra / Q000166:cytology; D020531:Subthalamic Nucleus / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C112429:2-(((3-(morpholinylmethyl)-2H-chromen-8-yl)oxy)methyl)morpholine; D001578:Benzopyrans; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D009025:Morpholines; D011725:Pyridines; D011758:Pyrroles; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; D026941:Sodium Channel Blockers; C065046:3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one; D012701:Serotonin; D013779:Tetrodotoxin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C056639:2-amino-5-phosphopentanoic acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D014633:Valine