Skip to main content
SpringerLink
Log in

Synaptic and Extrasynaptic Secretion of Serotonin

  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Serotonin is a major modulator of behavior in vertebrates and invertebrates and deficiencies in the serotonergic system account for several behavioral disorders in humans.

The small numbers of serotonergic central neurons of vertebrates and invertebrates produce their effects by use of two modes of secretion: from synaptic terminals, acting locally in “hard wired” circuits, and from extrasynaptic axonal and somatodendritic release sites in the absence of postsynaptic targets, producing paracrine effects.

In this paper, we review the evidence of synaptic and extrasynaptic release of serotonin and the mechanisms underlying each secretion mode by combining evidence from vertebrates and invertebrates. Particular emphasis is given to somatic secretion of serotonin by central neurons.

Most of the mechanisms of serotonin release have been elucidated in cultured synapses made by Retzius neurons from the central nervous system of the leech. Serotonin release from synaptic terminals occurs from clear and dense core vesicles at active zones upon depolarization. In general, synaptic serotonin release is similar to release of acetylcholine in the neuromuscular junction.

The soma of Retzius neurons releases serotonin from clusters of dense core vesicles in the absence of active zones. This type of secretion is dependent of the stimulation frequency, on L-type calcium channel activation and on calcium-induced calcium release.

The characteristics of somatic secretion of serotonin in Retzius neurons are similar to those of somatic secretion of dopamine and peptides by other neuron types. In general, somatic secretion by neurons is different from transmitter release from clear vesicles at synapses and similar to secretion by excitable endocrine cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Arango, V., Underwood, M. D., and Mann, J. J. (2002). Serotonin brain circuits involved in major depression and suicide. Prog. Brain. Res. 136:443–453.

    CAS  PubMed  Google Scholar 

  • Auger, C., and Marty, A. (2000). Quantal currents at single-site central synapses. J. Physiol. (Lond.) 526:3–11.

    Article  CAS  Google Scholar 

  • Baraban, J. M., and Aghajanian, G. K. (1981). Noradrenergic innervation of serotonergic neurons in the dorsal raphe: Demonstration by electron microscopic autoradiography. Brain. Res. 204:1–11.

    CAS  PubMed  Google Scholar 

  • Baumann, P. A., and Waldmeier, P. C. (1984). Negative feedback control of serotonin release in vivo: Comparison of 5-hydroxyindolacetic acid levels measured by voltammetry in conscious rats and by biochemical technique. Neuroscience 11:195–204.

    CAS  PubMed  Google Scholar 

  • Baumgarten, H. G., and Lachenmayer, L. (1985). Anatomical features and physiological properties of central serotonin neurons. 18(2):180–187.

    CAS  Google Scholar 

  • Beck, A., and Lohr, C. D. J. W. (2001). Calcium transients in subcompartments of the leech Retzius neuron as induced by single action potentials. J. Neurobiol. 48:1–18.

    CAS  PubMed  Google Scholar 

  • Becquet, D., Faudon, M., and Hery, F. (1990). The role of serotonin release and autoreceptors in the dorsalis raphe nucleus in the control of serotonin release in the cat caudate nucleus. Neuroscience 39:639–647.

    CAS  PubMed  Google Scholar 

  • Beltz, B., Eisen, J. S., Flamm, R., Harris-Warrick, R. M., Hooper, S. L., and Marder, E. (1984). Serotonergic innervation and modulation of the stomatogastric ganglion of three decapod crustaceans (Panulirus interruptus, Homarus americanus and Cancer irroratus). J. Exp. Biol. 109:35–54.

    CAS  PubMed  Google Scholar 

  • Betz, W. J., and Bewick, G. S. (1992). Optical analysis of synaptic vesicle recycling at the frog neuromuscular junction. Science 255:200–203.

    CAS  PubMed  Google Scholar 

  • Betz, W. J., Mao, F., and Bewick, G. S. (1992). Activity-dependent fluorescent staining and destaining of living vertebrate motor nerve terminals. J. Neurosci. 12:363–375.

    CAS  PubMed  Google Scholar 

  • Blier, P., Ramdine, R., Galzin, A. M., and Langer, S. Z. (1989). Frequency-dependence of serotonin autoreceptor but not alpha 2-adrenoceptor inhibition of [3H]-serotonin release in rat hypothalamic slices. Naunyn. Schmiedebergs. Arch. Pharmacol. 339:60–64.

    CAS  PubMed  Google Scholar 

  • Brieden, T., Ujeyl, M., and Naber, D. (2002). Psychopharmacological treatment of aggression in schizophrenic patients. Pharmacopsychiatry 35:83–89.

    CAS  PubMed  Google Scholar 

  • Brodfuehrer, P. D., Debski, E. A., O’Gara, B. A., and Friesen, W. O. (1995). Neuronal control of leech swimming. J. Neurobiol. 27:403–418.

    CAS  PubMed  Google Scholar 

  • Bruns, D., Engert, F., and Lux, H. D. (1993). A fast activating presynaptic reuptake current during serotonergic transmission in identified neurons of Hirudo. Neuron 10:559–572.

    CAS  PubMed  Google Scholar 

  • Bruns, D., and Jahn, R. (1995). Real-time measurement of transmitter release from single synaptic vesicles. Nature 377:62–65.

    CAS  PubMed  Google Scholar 

  • Bruns, D., Riedel, D., Klingauf, J., and Jahn, R. (2000). Quantal release of serotonin. Neuron 28:205–220.

    CAS  PubMed  Google Scholar 

  • Bunin, M. A., Prioleau, C., Mailman, R. B., and Wightman, R. M. (1998). Release and uptake rates of 5-hydroxytryptamine in the dorsal raphe and substantia nigra reticulata of the rat brain. J. Neurochem. 70:1077–1087.

    CAS  PubMed  Google Scholar 

  • Bunin, M. A., and Wightman, R. M. (1998). Quantitative evaluation of 5-hydroxytryptamine (serotonin) neuronal release and uptake: An investigation of extrasynaptic transmission. J. Neurosci. 18:4854–4860.

    CAS  PubMed  Google Scholar 

  • Bunin, M. A., and Wightman, R. M. (1999). Paracrine neurotransmission in the CNS: Involvement of 5-HT. Trends. Neurosci. 22:377–382.

    CAS  PubMed  Google Scholar 

  • Burrell, B. D., Sahley, C. L., and Muller, K. J. (2001). Non-associative learning and serotonin induce similar bi-directional changes in excitability of a neuron critical for learning in the medicinal leech. J. Neurosci. 21:1401–1412.

    CAS  PubMed  Google Scholar 

  • Chazal, G., and Ralston, J. J. I. (1987). Serotonin-containing structures in the nucleus raphe dorsalis of the cat: An ultrastructural analysis of dendrites, presynaptic dendrites, and axon terminals. J. Comp. Neurol. 259:317–329.

    CAS  PubMed  Google Scholar 

  • Chen, G., Gavin, P. F., Luo, G., and Ewing, A. G. (1995). Observation and quantitation of exocytosis from the cell body of a fully developed neuron in Planorbis corneus. J. Neurosci. 15:7747–7755.

    CAS  PubMed  Google Scholar 

  • Coggeshall, R. E. (1972). Autoradiographic and chemical localization of 5-hydroxytryptamine in identified neurons in the leech. Anat. Rec. 172:489–498.

    CAS  PubMed  Google Scholar 

  • Cooper, J. R., Bloom, F. E., and Roth, R. H. (1982). Serotonin (5-hydroxytriptamine). In: The biochemical bases of neuropharmacology. Oxford University Press, pp. 223–248.

  • Cooper, R. L., Fernandez de Miguel, F., Adams, W. B., and Nicholls, J. G. (1992). Anterograde and retrograde effects of synapse formation on calcium currents and neurite outgrowth in cultured leech neurons. Proc. Roy. Soc. Lond. B 249:217–222.

    CAS  Google Scholar 

  • Davalli, A. V., Biancardi, E., Pollo, A., Socci, C., Pontiroli, A. E., Pozza, G., Clementi, F., Sher, E., and Carbone, E. (1996). Dihidropyridine-sensitive and insensitive voltage-operated Ca2+ channels participate in the control of glucose-induced insulin release from human pancreatic beta cells. J. Endocrinol. 150:195–203.

    CAS  PubMed  Google Scholar 

  • De-Miguel, F. F., Vargas-Caballero, M., and García-Pérez, E. (2001). Spread of synaptic potentials through electrical synapses in Retzius neurones of the leech. J. Exp. Biol. 204:3241–3250.

    CAS  PubMed  Google Scholar 

  • Descarries, L., Watkins, K. C., Garcia, S., and Beaudet, A. (1982). The serotonin neurons in nucleus raphe dorsalis of adult rat: A light and electron microscope radioautographic study. J. Comp. Neurol. 207:239–254.

    CAS  PubMed  Google Scholar 

  • Dey, R. D., and Hoffpauir, J. M. (1986). Ultrastructural colocalization of the bioactive mediators 5-hydroxytryptamine and bombesin in endocrine cells of human fetal airways. Cell Tissue Res. 246:119–124.

    CAS  PubMed  Google Scholar 

  • Dietzel, I. D., Dreapeau, P., and Nicholls, J. G. (1986). Voltage dependence of 5-hydroxytryptamine release at a synapse between identified leech neurones in culture. J. Physiol. (Lond.) 372:191–205.

    CAS  Google Scholar 

  • Dixon, D., and Atwood, H. (1989). Cojoint action of phosphatidylinositol and adenylate cyclase systems in serotonin-induced facilitation at the crayfish neuromuscular junction. J. Neurophysiol. 62:1251–2159.

    CAS  PubMed  Google Scholar 

  • Drapeau, P., Melinyshyn, E., and Sanchez-Armass, S. (1989). Contact-mediated loss of the nonsynaptic response to transmitter during reinnervation of an identified leech neuron in culture. J. Neurosci. 9:2502–2508.

    CAS  PubMed  Google Scholar 

  • Drapeau, P., and Sanchez-Armass, S. (1988). Selection of postsynaptic serotonin receptors during reinnervation of an identified leech neuron in culture. J. Neurosci. 8:4718–4727.

    CAS  PubMed  Google Scholar 

  • Dun, N. J., and Minota, S. (1982). Post-tetanic depolarization in sympathetic neurones of the Guinea-pig. J. Physiol. (Lond.) 323:325–337.

    CAS  Google Scholar 

  • Edwards, D. H., Yeh, S. R., Musolf, B. E., Antonsen, B. L., and Krasne, F. B. (2002). Metamodulation of the crayfish escape circuit. Brain Behav. Evol. 360–369.

  • Fernández-De-Miguel, F., Cooper, R. L., and Adams, W. B. (1992). Synaptogenesis and calcium current distribution in cultured leech neurons. Proc. Roy. Soc. Lond. B 247:215–221.

    Google Scholar 

  • Fernández de Miguel, F., and Drapeau, P. (1995). Synapse formation and function: Insights from identified leech neurons in culture. J. Neurobiol. 27:367–379.

    CAS  PubMed  Google Scholar 

  • Ferris, C. F. (2000). Adolescent stress and neural plasticity in hamsters: A vasopressin-serotonin model of inappropriate aggressive behaviour. Exp. Physiol. Spec No: 85S–90S.

  • Fuchs, P. A., Henderson, L., and Nicholls, J. G. (1982). Chemical transmission between individual Retzius and sensory neurones of the leech in culture. J. Physiol. (Lond) 323:195–210.

    CAS  Google Scholar 

  • Fuxe, K. (1965). Evidence for the existence of monoamine neurons in the central nervous system. IV. Distribution of monoamine nerve terminals in the central nervous system. Acta. Physiol. Scand. 64:37+.

    Google Scholar 

  • Garcia-Perez, E., Vargas-Caballero, M., Velazquez-Ulloa, N., Minzoni, A., and De-Miguel, F. F. (2004). Synaptic integration in electrically coupled neurons. Biophys. J. 86:646–655.

    CAS  PubMed  Google Scholar 

  • Garris, P. A., Ciolkowski, E. L., Pastore, P., and Wightman, R. M. (1994). Efflux of dopamine from the synaptic cleft in the nucleus accumbens of the rat brain. J. Neurosci. 14:6084–6093.

    CAS  PubMed  Google Scholar 

  • Gilis, M. A., and Anctil, M. (2001). Monoamine release by neurons of a primitive nervous system: An amperometric study. J. Neurochem. 76:1774–1784.

    PubMed  Google Scholar 

  • Graeff, F. G., Guimaraes, F. S., De Andrade, T. G., and Deakin, J. F. (1996). Role of 5-HT in stress, anxiety, and depression. Pharmacol. Biochem. Behav. 54:129–141.

    CAS  PubMed  Google Scholar 

  • Groome, J. R., Clark, M., and Lent, C. M. (1993). The behavioural state of satiation in the leech is regulated by body destension and mimicked by serotonin depletion. J. Exp. Biol. 182:265–270.

    CAS  PubMed  Google Scholar 

  • Gross, C., Santarelli, L., Brunner, D., Zhuang, X., and Hen, R. (2000). Altered fear circuits in 5-HT(1A) receptor KO mice. Biol. Psychiatry 48:1157–1163.

    CAS  PubMed  Google Scholar 

  • Guo, X., Przywara, D. A., Wakade, T. D., and Wakade, A. R. (1996). Exocytosis coupled to mobilization of intracellular calcium by muscarine and caffeine in rat chromaffin cells. J. Neurochem. 67:155–162.

    CAS  PubMed  Google Scholar 

  • Henderson, L. (1983). The role of 5-hydroxytryptamine as a transmitter between identified leech neurones in culture. J. Physiol. (Lond) 339:311–326.

    Google Scholar 

  • Henderson, L. P., Kuffler, D. P., Nicholls, J. G., and Zhang, R. (1983). Structural and functional analysis of synaptic transmission between identified leech neurones in culture. J. Physiol. (Lond.) 340:347–358.

    CAS  Google Scholar 

  • Hery, F., and Ternaux, J. P. (1981). Regulation of release processes in central serotoninergic neurons. J. Physiol. (Paris) 77:287–301.

    CAS  Google Scholar 

  • Higley, J. D., and Linnoila, M. (1997). Low central nervous system serotonergic activity is traitlike and correlates with impulsive behavior. A nonhuman primate model investigating genetic and environmental influences on neurotransmission. Ann N.Y. Acad. Sci. 836:39–56.

    CAS  PubMed  Google Scholar 

  • Hornung, J. P. (2003). The human raphe nuclei and the serotonergic system. J. Chem. Neuroanat. 26:331–343.

    PubMed  Google Scholar 

  • Huang, L.-Y. M., and Neher, E. (1996). Ca2+-dependent exocytosis in the somata of dorsal root ganglion neurons. Neuron 17:135–145.

    CAS  PubMed  Google Scholar 

  • Hull, E. M., Lorrain, D. S., Du, J., Matuszewich, L., Lumley, L. A., Putnam, S. K., and Moses, J. (1999). Hormone-neurotransmitter interactions in the control of sexual behavior. Behav. Brain Res. 105:105–116.

    CAS  PubMed  Google Scholar 

  • Iravani, M. M., and Kruk, Z. L. (1997). Real-time measurement of stimulated 5-hydroxytryptamine release in rat substantia nigra pars reticulata brain slices. Synapse 25:93–102.

    CAS  PubMed  Google Scholar 

  • Jacobs, B. L., and Fornal, C. A. (1993). 5-HT and motor control: A hypothesis. Trends. Neurosci. 16:346–352.

    CAS  PubMed  Google Scholar 

  • Jaffe, E. H., Marty, A., Schulte, A., and Chow, R. H. (1998). Extrasynaptic vesicular transmitter release from the somata of substantia nigra neurons in rat midbrain slices. J. Neurosci. 18:3548–3553.

    CAS  PubMed  Google Scholar 

  • Jenike, M. A., Rauch, S. L., Cummings, J. L., Savage, C. R., and Goodman, W. K. (1996). Recent developments in neurobiology of obsessive-compulsive disorder. J. Clin. Psychiatry 57:492–503.

    CAS  PubMed  Google Scholar 

  • Jobe, P. C., Dailey, J. W., and Wernicke, J. F. (1999). A noradrenergic and serotonergic hypothesis of the linkage between epilepsy and affective disorders. Crit. Rev. Neurobiol. 13:317–356.

    CAS  PubMed  Google Scholar 

  • Kang, G., and Holz, G. G. (2003). Amplification of exocytosis by Ca2+-induced Ca2+ release in INS-1 pancreatic beta cells. J. Physiol. (Lond) 546:175–189.

    CAS  Google Scholar 

  • Kleinhaus, A. L., and Angstadt, J. D. (1995). Diversity and modulation of ionic conductances in leech neurons. J. Neurobiol. 27:419–433.

    CAS  PubMed  Google Scholar 

  • Kravitz, E. A. (1988). Hormonal control of behavior: Amines and the biasing of behavioral output in lobsters. Science 241:1775–1781.

    CAS  PubMed  Google Scholar 

  • Kravitz, E. A. (2000). Serotonin and aggression: Insights gained from a lobster model system and speculations on the role of amine neurons in a complex behavior. J. Comp. Physiol. [A] 186:221–238.

    CAS  Google Scholar 

  • Kristan, W. B., Jr. (1982). Sensory motor neurons responsible for the local bending response in leeches. J. Exp. Biol. 96:161–180.

    Google Scholar 

  • Kristan, W. B., and Nusbaum, M. P., Jr. (1983). The dual role of serotonin in leech swimming. J. Physiol. (Paris) 78:743–747.

    CAS  Google Scholar 

  • Kuffler, D. P., Nicholls, J. G., and Drapeau, P. (1987). Transmitter localization and vesicle turnover at a serotoninergic synapse between identified leech neurons in culture. J. Comp. Neurol. 256:516–526.

    CAS  PubMed  Google Scholar 

  • Lemmens, R., Larsson, O., Berggren, P. O., and Islam, M. S. (2001). Ca2+-induced Ca2+ release from the endoplasmic reticulum amplifies the Ca2+ signal mediated by activation of voltage-gated L-type Ca2+ channels in pancreatic beta-cells. J. Biol. Chem. 276:9971–9977.

    CAS  PubMed  Google Scholar 

  • Lent, C. M. (1973). Retzius Cells: Neuroeffectors controlling mucus release by the leech. Science 179:693–696.

    CAS  PubMed  Google Scholar 

  • Lent, C. M. (1985). Serotonergic modulation of the feeding behavior of the medicinal leech. Brain. Res. Bull. 14:643–655.

    CAS  PubMed  Google Scholar 

  • Lent, C. M., and Dickinson, M. H. (1984). Serotonin integrates the feeding behavior of the medicinal leech. J. Comp. Physiol. A 154:457–471.

    CAS  Google Scholar 

  • Lent, C. M., and Frazer, B. M. (1977). Connectivity of the monoamine-containing neurones in central nervous system of leech. Nature 266:844–847.

    CAS  PubMed  Google Scholar 

  • Lesch, K. P., and Merschdorf, U. (2000). Impulsivity, aggression, and serotonin: A molecular psychobiological perspective. Behav. Sci. Law. 18:581–604.

    CAS  PubMed  Google Scholar 

  • Lessman, V., and Dietzel, I. D. (1995). Two kinetically distinct 5-Hidroxytryptamine-activated Cl- conductances at Retzius P-cell synapses of the medicinal leech. J. Neurosci. 15:1496–1505.

    PubMed  Google Scholar 

  • Lessmann, V., and Dietzel, I. D. (1991). Development of serotonin-induced ion currents in identified embryonic Retzius cells from the medicinal leech (Hirudo medicinalis). J. Neurosci. 11:800–809.

    CAS  PubMed  Google Scholar 

  • Liem, R. S., and Copray, J. C. (1996). Immunogold localization of serotonin within synaptic terminals in the rat mesencephalic trigeminal nucleus. Acta. Anat. (Basel) 155:50–56.

    CAS  Google Scholar 

  • Liposits, Z., Gorcs, T., and Trombitas, K. (1985). Ultrastructural analysis of central serotoninergic neurons immunolabeled by silver-gold-intensified diaminobenzidine chromogen. Completion of immunocytochemistry with X-ray microanalysis. J. Histochem. Cytochem. 33:604–610.

    CAS  PubMed  Google Scholar 

  • Lockery, S. R., and Kristan, W. B., Jr. (1990). Distributed processing of sensory information in the leech II. Identification of interneurons contributing to the local bending reflex. J. Neurosci. 10:1816–1829.

    CAS  PubMed  Google Scholar 

  • Lockery, S. R., and Kristan, W. B., Jr. (1991). Two forms of sensitization of the local bending reflex of the medicinal leech. J. Comp. Physiol. [A] 168:165–177.

    CAS  Google Scholar 

  • Loizou, L. A. (1972). The postnatal ontogeny of monoamine-containing neurones in the central nervous system of the albino rat. Brain. Res. 40:395–418.

    CAS  PubMed  Google Scholar 

  • Lundberg, F. M., and Hökfelt, T. (1983). Coexistence of peptides and classical neurotransmitters. Trends Neurosci. 6:325–333.

    CAS  Google Scholar 

  • Mansvelder, H. D. Y. K. K. S. (2000). Regulation of exocytosis in neuroendocrine cells: Spatial organization of channels and vesicles, stimulus-secretion coupling, Ca2+ buffers and modulation. Prog. Neurobiol. 62:427–441.

    CAS  PubMed  Google Scholar 

  • Mar, A., and Drapeau, P. (1996). Modulation of conduction block in leech mechanosensory neurons. J. Neurosci. 16:4335–4343.

    CAS  PubMed  Google Scholar 

  • Marder, E., and Eisen, J. S. (1984). Electrically coupled pacemaker neurons respond differently to same physiological inputs and neurotransmitters. J. Neurophysiol. 51:1362–1374.

    CAS  PubMed  Google Scholar 

  • Marlier, L., Sandillon, F., Poulat, P., Rajaofetra, N., Geffard, M., and Privat, A. (1991). Serotonergic innervation of the dorsal horn of rat spinal cord: Light and electron microscopis immunocytochemical study. J. Neurocytol. 20:320–322.

    Google Scholar 

  • Martin, G. R., and Humphrey, P. P. (1994). Receptors for 5-hydroxytryptamine: Current perspectives on classification and nomenclature. Neuropharmacology 33:261–273.

    Article  CAS  PubMed  Google Scholar 

  • Mosko, S. S., Haubrich, D., and Jacobs, B. L. (1977). Serotonergic afferents to the dorsal raphe nucleus: Evdience from HRP and synaptosomal uptake studies. Brain Res. 119:269–290.

    CAS  PubMed  Google Scholar 

  • Moukhles, H., Bosler, O., Bolam, J. P., Vallee, A., Umbriaco, D., Geffard, M., and Doucet, G. (1997). Quantitative and morphometric data indicate precise cellular interactions between serotonin terminals and postsynaptic targets in rat substantia nigra. Neuroscience 76:1159–1171.

    CAS  PubMed  Google Scholar 

  • Neijt, H. C., Plomp, J. J., and Vijverberg, H. P. (1989). Kinetics of the membrane current mediated by serotonin 5-HT3 receptors in cultured mouse neuroblastoma cells. J. Physiol. (Lond.) 411:257–269.

    CAS  Google Scholar 

  • Nguyen, D., and Sargent, P. B. (2002). Synaptic vesicle recycling at two classes of release sites in giant nerve terminals of the embryonic chicken ciliary ganglion. J. Comp. Neurol. 24:128–137.

    Google Scholar 

  • Nicholls, J. G., and Kuffler, D. P. (1990). Quantal release of serotonin from presynaptic nerve terminals. Neurochem. Int. 17:157–163.

    CAS  Google Scholar 

  • Nusbaum, M. P. (1986). Synaptic basis of swim initiation in the leech. III. Synaptic effects of serotonin-containing interneurones (cells 21 and 61) on swim CPG neurones (cells 18 and 208). J. Exp. Biol. 122:303–321.

    CAS  PubMed  Google Scholar 

  • Nusbaum, M. P., Friesen, W. O., Kristan, W. B., Jr., and Pierce, R. A. (1987). Neural mechanisms generating the leech swimming rhythm. J. Comp. Physiol. A 161A:355–366.

    Google Scholar 

  • Nusbaum, M. P., and Kristan, W. B. J. (1986). Swim initiation in the leech by serotonin-containing interneurons cells 21 and 61. J. Exp. Biol. 122:277–302.

    CAS  PubMed  Google Scholar 

  • Peters, J. A., Malone, H. M., and Lambert, J. J. (1993). An electrophysiological investigation of the properties of 5-HT3 receptors of rabbit nodose ganglion neurones in culture. Br. J. Pharmacol. 110:665–676.

    CAS  PubMed  Google Scholar 

  • Portas, C. M., Bjorvatn, B., and Ursin, R. (2000). Serotonin and the sleep/wake cycle: Special emphasis on microdialysis studies. Prog. Neurobiol. 60:13–35.

    CAS  PubMed  Google Scholar 

  • Puopolo, M., Hochstetler, S. E., Gustincich, S., Wightman, R. M., and Raviola, E. (2001). Extrasynaptic release of dopamine in a retinal neuron: Activity dependence and transmitter modulation. Neuron 30:211–225.

    CAS  PubMed  Google Scholar 

  • Raleigh, M. J., McGuire, M. T., Brammer, G. L., Pollack, D. B., and Yuwiler, A. (1991). Serotonergic mechanisms promote dominance acquisition in adult male vervet monkeys. Brain. Res. 559:181–190.

    CAS  PubMed  Google Scholar 

  • Ressler, K. J., and Nemeroff, C. B. (2000). Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depress. Anxiet. 12:2–19.

    Google Scholar 

  • Reuter, H. (1996). Diversity and function of presynaptic calcium channels in the brain. Curr. Opin. Neurobiol. 6:331–337.

    CAS  PubMed  Google Scholar 

  • Richards, K. S., Simon, D. J., Pulver, S. R., Beltz, B. S., and Marder, E. (2003). Serotonin in the developing stomatogastric system of the lobster, Homarus americanus. J. Neurobiol. 54:380–392.

    CAS  PubMed  Google Scholar 

  • Ridet, J. L., Rajaofetra, N., Teilhac, J. R., Geffard, M., and Privat, A. (1993). Evidence for nonsynaptic serotonergic and noradrenergic innervation of the rat dorsal horn and possible involvement of neuron-glia interactions. Neuroscience 52:143–157.

    CAS  PubMed  Google Scholar 

  • Ridet, J. L., Tamir, H., and Privat, A. (1994). Direct immunocytochemical locallization of 5-hydroxytryptamine receptors in the adult rat spinal cord: A light and electron microscopic study using an anti-idiotypic antiserum. J. Neurosci. Res. 38:109–121.

    CAS  PubMed  Google Scholar 

  • Rio, J. P., Reperant, J., Miceli, D., Medina, M., and Kenigfest-Rio, N. (2002). Serotonergic innervation of the isthmo-optic nucleus of the pigeon centrifugal visual system. An immunocytochemical electron microscopic study. Brain. Res. 924:127–131.

    CAS  PubMed  Google Scholar 

  • Rogawski, M. A., and Aghajanian, G. K. (1981). Serotonin autoreceptors on dorsal raphe neurons: Structure-activity relationships of tryptamine analogs. J. Neurosci. 1:1148–1154.

    CAS  PubMed  Google Scholar 

  • Sahley, C. L. (1994). Serotonin depletion impairs but does not eliminate classical conditioning in the leech Hirudo medicinalis. Behav. Neurosci. 108:1043–1052.

    CAS  PubMed  Google Scholar 

  • Sahley, C. L. (1995). What we have learned from the study of learning in the leech. J. Neurobiol. 27:434–445.

    CAS  PubMed  Google Scholar 

  • Sakurai, A., and Katz, P. S. (2003). Spike timing-dependent serotonergic neuromodulation of synaptic strength intrinsic to a central pattern generator circuit. J. Neurosci. 23:10745–10755.

    CAS  PubMed  Google Scholar 

  • Saller, C. F., and Stricker, E. M. (1976). Hyperphagia and increased growth in rats after intraventricular injection of 5,7-dihydroxytryptamine. Science 192:385–387.

    CAS  PubMed  Google Scholar 

  • Sanchez-Armass, S., Merz, D. C., and Drapeau, P. (1991). Distinct receptors, second messengers and conductances underlying the dual responses to serotonin in an identified leech neurone. J. Exp. Biol. 155:531–547.

    CAS  PubMed  Google Scholar 

  • Satterlie, R. A., and Norekian, T. P. (1996). Modulation of swimming speed in the pteropod mollusc, Clione limacina: role of a compartmental serotonergic system. Invert. Neurosci. 2:157–165.

    CAS  PubMed  Google Scholar 

  • Satterlie, R. A., Norekian, T. P., and Pirtle, T. J. (2000). Serotonin-induced spike narrowing in a locomotor pattern generator permits increases in cycle frequency during accelerations. J. Neurophysiol. 83:2163–2170.

    CAS  PubMed  Google Scholar 

  • Sawada, M., and Coggeshall, R. E. (1976b). A central inhibitory action of 5-hydroxytryptamine in the leech. J. Neurobiol. 7:477–482.

    CAS  Google Scholar 

  • Schwartz, J. H., and Shkolnik, L. J. (1981). The giant serotonergic neuron of Aplysia: A multi-targeted nerve cell. J. Neurosci. 1:606–619.

    CAS  PubMed  Google Scholar 

  • Smiley, J. F., and Goldman-Rakic, P. S. (1996). Serotonergic axons in monkey prefrontal cerebral cortex synapse predominantly on interneurons as demonstrated by serial section electron microscopy. J. Comp. Neurol. 367:431–443.

    CAS  PubMed  Google Scholar 

  • Soldo, B. L., Giovannucci, D. R., Stuenkel, E. L., and Moises, H. C. (2004). Ca(2+) and frequency dependence of exocytosis in isolated somata of magnocellular supraoptic neurones of the rat hypothalamus. J. Physiol. (Lond.) 555:699–711.

    CAS  Google Scholar 

  • Starkey, S. J., and Skingle, M. (1994). 5-HT1D as well as 5-HT1A autoreceptors modulate 5-HT release in the guinea-pig dorsal raphe nucleus. Neuropharmacology 33:393–402.

    CAS  PubMed  Google Scholar 

  • Stauderman, K. A., and Jones, D. J. (1986). Presynaptic serotonin receptors regulate [3H]serotonin release from rat spinal cord synaptosomes. Eur. J. Pharmacol. 120:107–109.

    CAS  PubMed  Google Scholar 

  • Stewart, R. R., Adams, W. B., and Nicholls, J. G. (1989). Presynaptic calcium currents and facilitation of serotonin release at synapses between cultured leech neurones. J. Exp. Biol. 144:1–12.

    CAS  PubMed  Google Scholar 

  • Sugita, S., Shen, K. Z., and North, R. A. (1992). 5-hydroxytryptamine is a fast excitatory transmitter at 5-HT3 receptors in rat amygdala. Neuron 8:199–203.

    CAS  PubMed  Google Scholar 

  • Szczupak, L., and Kristan, W. B., Jr. (1995). Widespread mechanosensory activation of the serotonergic system of the medicinal leech. J. Neurophysiol. 74:2614–2624.

    CAS  PubMed  Google Scholar 

  • Trueta, C., Mendez, B., and De-Miguel, F. F. (2003). Somatic exocytosis of serotonin mediated by L-type calcium channels in cultured leech neurones. J. Physiol. (Lond.) 547:405–416.

    CAS  Google Scholar 

  • Trueta, C., Morales, M. A., Sanchez-Armass, S., and De-Miguel, F. F. (2004). Calcium-induced calcium release contributes to somatic secretion of serotonin in leech retzius neurons. J. Neurobiol. 61:309–316.

    CAS  PubMed  Google Scholar 

  • Trulson, M. E., and Frederickson, C. J. (1987). A comparison of the electrophysiological and pharmacological properties of serotonin-containing neurons in the nucleus raphe dorsalis, raphe medianus and raphe pallidus recorded from mouse brain slices in vitro: Role of autoreceptors. Brain Res. Bull. 18:179–190.

    CAS  PubMed  Google Scholar 

  • Ursin, R. (2002). Serotonin and sleep. Sleep Med. Rev. 6:55–69.

    PubMed  Google Scholar 

  • Van Bockstaele, E. J., Cestari, D. M., and Pickel, V. M. (1994). Synaptic structure and connectivity of serotonin terminals in the ventral tegmental area: Potential sites for modulation of mesolimbic dopamine neurons. Brain. Res. 647:307–322.

    CAS  PubMed  Google Scholar 

  • Velazquez-Ulloa, N., Blackshaw, S. E., Szczupak, L., Trueta, C., Garcia, E., and De-Miguel, F. F. (2003). Convergence of mechanosensory inputs onto neuromodulatory serotonergic neurons in the leech. J. Neurobiol. 54:604–617.

    PubMed  Google Scholar 

  • Walz, W., and Schlue, W. R. (1982). Ionic mechanism of a hyperpolarizing 5-hydroxytryptamine effect on leech neuropile glial cells. Brain. Res. 250:111–121.

    CAS  PubMed  Google Scholar 

  • Weiger, W. A. (1997). Serotonergic modulation of behaviour: A phylogenetic overview. Biol. Rev. Camb. Philos. Soc. 72:61–95.

    CAS  PubMed  Google Scholar 

  • Willard, A. L. (1981). Effects of serotonin on the generation of the motor program for swimming by the medicinal leech. J. Neurosci. 1:936–944.

    CAS  PubMed  Google Scholar 

  • Wilson, R. J., Kristan, W. B., Jr., and Kleinhaus, A. L. (1996). An increase in activity of serotonergic Retzius neurones may not be necessary for the consummatory phase of feeding in the leech Hirudo medicinalis. J. Exp. Biol. 199:1405–1414.

    CAS  PubMed  Google Scholar 

  • Yang, J., Mathie, A., and Hille, B. (1992). 5-HT3 receptor channels in dissociated rat superior cervical ganglion neurons. J. Physiol. (Lond.) 448:237–256.

    CAS  Google Scholar 

  • Zaidi, Z. F., and Matthews, M. R. (1997). Exocytotic release from neuronal cell bodies, dendrites and nerve terminals in sympathetic ganglia of the rat, and its differential regulation. Neuroscience 80:861–891.

    CAS  PubMed  Google Scholar 

  • Zaidi, Z. F., and Matthews, M. R. (1999). Stimulant-induced exocytosis from neuronal somata, dendrites, and newly formed synaptic nerve terminals in chronically decentralized sympathetic ganglia of the rat. J. Comp. Neurol. 415:121–143.

    CAS  PubMed  Google Scholar 

  • Zangrossi, H., Jr., Viana, M. B., Zanoveli, J., Bueno, C., Nogueira, R. L., and Graeff, F. G. (2001). Serotonergic regulation of inhibitory avoidance and one-way escape in the rat elevated T-maze. Neurosci. Biobehav. Rev. 25:637–645.

    CAS  PubMed  Google Scholar 

  • Zimmermann, H. (1993). Synaptic transmission. Cellular and molecular bases. Georg Thieme Verlag. Stuttgart-New York; Oxford University Press, New York.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departamento de Biofísica, Instituto de Fisiología Celular, Universidad NacionalAut ónoma deMéxico, 04510, México, D.F., México

    Francisco F. De-Miguel

  2. Departamento de Neurofisiología, Instituto Nacional de Psiquiatría, Calzada México-Xochimilco 101, 14390, D.F., México

    Citlali Trueta

  3. Instituto de Fisiología Celular, UNAM., Apartado Postal 70-253., C.P. 04510, D.F., México

    Francisco F. De-Miguel

Authors
  1. Francisco F. De-Miguel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Citlali Trueta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Francisco F. De-Miguel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

De-Miguel, F.F., Trueta, C. Synaptic and Extrasynaptic Secretion of Serotonin. Cell Mol Neurobiol 25, 297–312 (2005). https://doi.org/10.1007/s10571-005-3061-z

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-005-3061-z

Keywords

Search

Navigation