SYNAPTIC VESICLE DEPLETION IN RETICULOSPINAL AXONS IS REDUCED BY 5-HYDROXYTRYPTAMINE - DIRECT EVIDENCE FOR PRESYNAPTIC MODULATION OF GLUTAMATERGIC TRANSMISSION

5-hydroxytryptamine (5-HT; serotonin) is known to depress glutamatergi c synaptic transmission in the spinal cord of vertebrates. To test dir ectly whether 5-HT inhibits synaptic glutamate release, we examined it s effect on the ultrastructure of synaptic vesicle clusters in giant r eticulospinal axons in a lower vertebrate (lamprey; Lampetra fluviatil is). The size of these axons makes it possible to selectively expose o nly a part of the presynaptic element to 5-HT, while another part of t he same axon is maintained in control solution. Action potential stimu lation at 20 Hz for 20 min caused a marked reduction in the number of synaptic vesicles in active zones maintained in control solution, whil e in the part exposed to 5-HT (20 mu M) the number of synaptic vesicle s per active zone was similar to 3-fold higher. In contrast, 5-HT had no effect on the number of vesicles in resting axons. To examine wheth er 5-HT acts by reducing presynaptic Ca2+ influx, intra-axonal recordi ngs of Ba2+ potentials were performed. No reduction of the axonal Ba2 potential could be detected after application of 20 or 200 mu M 5-HT. The present results show that 5-HT reduces the rate of synaptic exocy tosis in reticulospinal axons. The effect appears to be mediated by a mechanism distinct from the presynaptic Ca2+ channels.