PRESYNAPTIC INHIBITION BY SEROTONIN OF GLYCINERGIC INHIBITORY SYNAPTIC CURRENTS IN THE RAT-BRAIN STEM

1. With the use of a thin brain stem slice preparation, we recorded in visualized neonatal rat hypoglossal motoneurons unitary glycinergic i nhibitory postsynaptic currents (IPSCs) that were evoked by extracellu lar stimulation of nearby interneurons. We found that 10 mu M serotoni n (5-HT) presynaptically inhibited this glycinergic synaptic transmiss ion by 85.5%. 2. In the somata of presynaptic interneurons. 5-HT1A rec eptor activation potentiated inwardly rectifying K+ channels and inhib ited voltage-activated calcium channels. 3. In contrast, the 5-HT1B re ceptor was primarily responsible for inhibition of evoked glycinergic IPSCs; a selective 5-HT1B receptor agonist, N-(3-trifluoromethylphenyl ) piperazine (TFMPP, 10 mu M), inhibited synaptic transmission by 97.3 %. On the other hand, 5-HT1A receptor activation by (+)-8-OH-dipropyla minotetralin (8-OHDPAT, 1 mu M) inhibited IPSCs by only 24.1%. A 5-HT1 A antagonist, hyoxyphenyl)-4-[4-(2-phthalimido)-butyl]piperazine hydro bromide (NAN-190, 1 mu M), had no effect on synaptic inhibition by 5-H T. 4. In the presence of tetrodotoxin (TTX) as well as TTX with cadmiu m (50 mu M), we found that 5-HT1B receptor activation by TFMPP reduced the frequency of spontaneous miniature IPSCs (mIPSCs) without changin g their mean amplitude. The results suggested that the 5-HT1B receptor s activated at the presynaptic terminal inhibited synaptic transmissio n independent of inhibiting calcium influx through voltage-activated c alcium channels. 5. These results indicate that activation of inwardly rectifying K+ channels and inhibition of voltage-activated calcium ch annels by 5-HT1A receptor activation do not constitute a main pathway for presynaptic inhibition by 5-HT of glycinergic synaptic transmissio n. Modulation of the transmitter release mechanism through 5-HT1B rece ptor activation may, at least in part, contribute to presynaptic inhib ition by 5-HT.