PRESYNAPTIC INHIBITION OF GLUTAMATERGIC SYNAPTIC TRANSMISSION TO RAT MOTONEURONS BY SEROTONIN

1. In a brain stem slice preparation, we recorded glutamatergic excita tory postsynaptic currents (EPSCs) in hypoglossal motoneurons (HMs) ev oked by extracellular stimulation in the reticular formation just ipsi lateral to the hypoglossal motor nucleus (n. XII). Serotonin (5-HT) in hibited glutamatergic synaptic transmission in a dose-dependent fashio n as indicated by a reduction in the evoked EPSC (eEPSC) peak amplitud e to 46 +/- 2% (mean +/- SE, n = 26) of control (5-HT 10 mu M). This e ffect was not voltage dependent, as the eEPSC reversal potential was n ot altered (n = 5). Additionally, 5-HT decreased the rate of rise of t he eEPSC to 41 +/- 2% of control (n = 14). Blockade of N-methyl-D-aspa rtate-receptor-channels by D(-) -2-amino-5-phosphonopentanoic acid (50 mu M) or of a lpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid /kainate receptor-channels by 6,7-dinitro-quinoxaline (20 mu M) did no t alter the relative reduction of the eEPSC amplitude by 5-HT (n = 7 a nd 3, respectively), 2. In the presence of tetrodotoxin (1 mu M), bath application of 5-HT did not reduce postsynaptic glutamate currents el icited by pressure ejection of L-glutamate (1 mM) onto HMs (n = 5), an d it increased the median interevent interval of spontaneous miniature EPSCs (mEPSCs) to 178 +/- 12% of control (n = 4), suggesting that 5-H T acts presynaptically to reduce the probability of vesicle release. m EPSC amplitude was decreased slightly in three of four cells (median a mplitude = 92 +/- 3% of control). 3. The specific 5-HT1B receptor agon ist [3-(1,2,5,6-tetrahydropyrid-4-yl) pyrrolo[3,2-b]pyrid-5-one] (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 interevent interval incre ased to 231 +/- 36% of control; median mEPSC amplitude = 102 +/- 3% of control, n = 5). Additionally, 5-HT-mediated inhibition was not block ed by coapplication of 1-(2-methoxyphenyl)-4-[4-(2-phthalimido) butyl] piperazine hydrobromide (1 mu M), a 5-HT1A antagonist, and l)-1-piper dinyl]ethyl]-2,4(1H,3H)-quinazolinedione tartrate (1 mu M), a 5-HT2A/2 C antagonist (n = 4). These data indicate that the 5-HT effect is prim arily 5-HT1B receptor mediated. 4. We conclude that 5-HT, acting throu gh presynaptic 5-HT1B receptors, inhibits glutamatergic synaptic trans mission by reducing the probability of vesicle release.