PRESYNAPTIC INHIBITION OF GLUTAMATERGIC SYNAPTIC TRANSMISSION TO RAT MOTONEURONS BY SEROTONIN. Singer, Joshua H., Mark C. Bellingham, and Albert J. Berger. Department of Physiology & Biophysics, University of Washington School of Medicine, Box 357290, Seattle, Washington USA 98195-7290.
APStracts 3:0057N, 1996.
SUMMARY AND CONCLUSIONS
1) In a brain stem slice preparation, we recorded glutamatergic excitatory postsynaptic currents (EPSCs) in hypoglossal motoneurons (HMs) evoked by extracellular stimulation in the reticular formation just ipsilateral to the hypoglossal motor nucleus (n. XII). Serotonin (5-HT) inhibited glutamatergic synaptic transmission in a dose-dependent fashion as indicated by a reduction in the evoked EPSC (eEPSC) peak amplitude to 46 +/- 2% (mean +/- SEM, n = 26) of control (5-HT 10 [mu]M). This effect was not voltage dependent, as the eEPSC reversal potential was not altered (n = 5). Additionally, 5-HT decreased the rate of rise of the eEPSC to 41 +/- 2% of control (n = 14). Blockade of NMDA receptor-channels by D(-)-2-amino-5-phosphonopentanoic acid (AP-5, 50 [mu]M), or of AMPA/kainate receptor-channels by 6,7-dinitro-quinoxaline (DNQX, 20 [mu]M), did not alter the relative reduction of the eEPSC amplitude by 5-HT (n = 7 and 3, respectively). 2) In the presence of tetrodotoxin (TTX, 1 [mu]M), bath application of 5-HT did not reduce postsynaptic glutamate currents elicited by pressure ejection of L-glutamate (1 mM) onto HMs (n = 5), and it increased the median inter-event interval of spontaneous miniature EPSCs (mEPSCs) to 178 +/- 12% of control (n ? = ? 4), suggesting that 5-HT acts presynaptically to reduce the probability of vesicle release. Miniature EPSC amplitude was decreased slightly in 3 of 4 cells (median amplitude = 92 +/- 3% of control). 3) The specific 5-HT 1B receptor agonist [3-(1,2,5,6- tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one] (CP-93,129, 1 [mu] M) mimicked 5-HT in its effect on eEPSCs (eEPSC amplitude reduced to 31 +/- 5% of control; rate of rise reduced to 40 +/- 4 % of control, n = 10 and 5, respectively) and mEPSCs (median inter-event interval increased to 231 +/- 36% of control; median mEPSC amplitude = 102 +/- 3% of control, n = 5). Additionally, 5-HT- mediated inhibition was not blocked by co-application of 1-(2-methoxyphenyl)- 4-[4-(2-phthalimido) butyl] piperazine hydrobromide (NAN-190, 1 [mu]M), a 5-HT 1A antagonist, and 3-[2-[4-(4-flurobenzoyl)-1-piperdinyl]ethyl]-2,4(1H,3H)- quinazolinedione tartrate (ketanserin, 1 [mu]M), a 5-HT 2A/2C antagonist (n = 4). These data indicate that the 5-HT effect is primarily 5-HT 1B receptor mediated. 4) We conclude that 5-HT, acting through presynaptic 5-HT 1B receptors, inhibits glutamatergic synaptic transmission by reducing the probability of vesicle release.

Received 26 December 1995; accepted in final form 8 March 1996.
APS Manuscript Number J862-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 27 March 96