1. 5-HT1B Receptor-Mediated Presynaptic Inhibition of GABA Release in the Suprachiasmatic Nucleus
- Author
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F. Edward Dudek, Patricia J. Sollars, Gary E. Pickard, and Jayne R. Bramley
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Male ,Agonist ,Patch-Clamp Techniques ,Time Factors ,Pyridines ,Physiology ,medicine.drug_class ,Presynaptic Terminals ,Tetrodotoxin ,In Vitro Techniques ,Bicuculline ,Serotonergic ,Inhibitory postsynaptic potential ,Membrane Potentials ,GABA Antagonists ,Rats, Sprague-Dawley ,Mice ,Glutamatergic ,Quinoxalines ,Excitatory Amino Acid Agonists ,medicine ,Animals ,Drug Interactions ,Pyrroles ,gamma-Aminobutyric Acid ,Mice, Knockout ,Neurons ,GABAA receptor ,Suprachiasmatic nucleus ,Chemistry ,General Neuroscience ,Neural Inhibition ,Valine ,Rats ,Serotonin Receptor Agonists ,nervous system ,Receptor, Serotonin, 5-HT1B ,GABAergic ,Suprachiasmatic Nucleus ,sense organs ,Excitatory Amino Acid Antagonists ,Neuroscience ,medicine.drug - Abstract
The suprachiasmatic nucleus (SCN) receives a dense serotonergic innervation that modulates photic input to the SCN via serotonin 1B (5-HT1B) presynaptic receptors on retinal glutamatergic terminals. However, the majority of 5-HT1B binding sites in the SCN are located on nonretinal terminals and most axonal terminals in the SCN are GABAergic. We therefore tested the hypothesis that 5-HT1B receptors might also be located on SCN GABAergic terminals by examining the effects of the highly selective 5-HT1B receptor agonist CP-93,129 on SCN miniature inhibitory postsynaptic currents (mIPSCs). Whole cell patch-clamp recordings of mIPSCs were obtained from rat and mouse SCN neurons in hypothalamic slices. Using CsCl-containing microelectrodes with QX314, we isolated mPSCs that were sensitive to the GABAA receptor antagonist, bicuculline. Bath application of CP-93,129 (1 μM) decreased the frequency of mIPSCs by an average of 22% ( n = 7) in rat SCN neurons and by an average of 30% ( n = 8) in mouse SCN neurons with no clear effect on mIPSC amplitude. In mice lacking functional 5-HT1B receptors, CP-93,129 (1 μM) had no clear effect on the frequency or the amplitude of mIPSCs recorded in any of the cells tested ( n = 4). The decrease in the frequency of mIPSCs of SCN neurons produced by the selective 5-HT1B receptor agonist CP-93,129 is consistent with the interpretation that 5-HT1B receptors are located on GABA terminals in the SCN and that 5-HT inhibits GABA release via a 5-HT1B presynaptic receptor-mediated mechanism.
- Published
- 2005
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