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 glutamatergic synaptic transmission in the spinal cord of vertebrates. To test directly whether 5-HT inhibits synaptic glutamate release, we examined its effect on the ultrastructure of synaptic vesicle clusters in giant reticulospinal axons in a lower vertebrate (lamprey; Lampetra fluviatilis). The size of these axons makes it possible to selectively expose only a part of the presynaptic element to 5-HT, while another part of the same axon is maintained in control solution. Action potential stimulation at 20 Hz for 20 min caused a marked reduction in the number of synaptic vesicles in active zones maintained in control solution, while in the part exposed to 5-HT (20 microM) the number of synaptic vesicles per active zone was approximately 3-fold higher. In contrast, 5-HT had no effect on the number of vesicles in resting axons. To examine whether 5-HT acts by reducing presynaptic Ca2+ influx, intra-axonal recordings of Ba2+ potentials were performed. No reduction of the axonal Ba2+ potential could be detected after application of 20 or 200 microM 5-HT. The present results show that 5-HT reduces the rate of synaptic exocytosis in reticulospinal axons. The effect appears to be mediated by a mechanism distinct from the presynaptic Ca2+ channels.
Shupliakov
O
O
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Pieribone
V A
VA
Gad
H
H
Brodin
L
L
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001369:Axons / Q000187:drug effects; D001464:Barium / Q000494:pharmacology; D002452:Cell Count; D005089:Exocytosis / Q000187:drug effects*; D018698:Glutamic Acid / Q000378:metabolism*; D007798:Lampreys; D017729:Presynaptic Terminals / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology*; D013116:Spinal Cord / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D001464:Barium; D012701:Serotonin; D018698:Glutamic Acid; D013779:Tetrodotoxin