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J Neurophysiol 93: 3157-3164, 2005. First published February 16, 2005; doi:10.1152/jn.00770.2004
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5-HT1B Receptor-Mediated Presynaptic Inhibition of GABA Release in the Suprachiasmatic Nucleus

Jayne R. Bramley, Patricia J. Sollars, Gary E. Pickard and F. Edward Dudek

Department of Biomedical Sciences, Anatomy and Neurobiology Section, Colorado State University, Fort Collins, Colorado

Submitted 29 July 2004; accepted in final form 11 February 2005

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.


Address for reprint requests and other correspondence: G. E. Pickard, Dept. of Biomedical Sciences, Anatomy and Neurobiology Section, Colorado State University, Fort Collins, CO 80523 (E-mail: gary.pickard{at}colostate.edu)




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