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Serotonergic innervation of the dorsal horn of rat spinal cord: light and electron microscopic immunocytochemical study

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Journal of Neurocytology

Summary

The ultrastructure of serotonergic projections to the dorsal horn of the rat spinal cord has been investigated, using a highly specific polyclonal antiserum. The highest concentrations of immunoreactive profiles were found in lamina I and the outer part of lamina II (IIo). Intermediate concentrations were found in laminae III and IV, while the inner part of lamina II (IIi) was almost devoid of immunoreactivity. Whereas 60% of the profiles show at least one varicosity studded with synaptic vesicles, only one-fifth of the latter contributes to classical synapses, the remaining profiles being devoid of a facing postsynaptic density. The results are compared with those in the literature and our own results relative to other regions of the cord. It is concluded that the pauci-synaptic projections to the dorsal horn could correspond to a diffuse influence of serotonin, the targets for which are determined by the corresponding serotonergic receptors.

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References

  • Barasi, S. &Roberts, M. H. T. (1974) The modulation of lumbar motoneurone excitability by stimulation of a putative 5-hydroxytryptamine pathway.British Journal of Pharmacology 52, 339–48.

    PubMed  Google Scholar 

  • Barber, R. P., Vaughn, J. E. &Roberts, E. (1982) The cytoarchitecture of GABAergic neurons in the rat spinal cord.Brain Research 238, 305–28.

    PubMed  Google Scholar 

  • Basbaum, A. I., Clanton, C. H. &Fields, H. L. (1978) Three bulbospinal pathways from the rostral medulla of the cat: an autoradiographic study of pain modulating systems.Journal of Comparative Neurology 178, 209–24.

    PubMed  Google Scholar 

  • Basbaum, A. I. &Fields, H. L. (1979) The origin of descending pathways in the dorsolateral funiculus of the spinal cord of the cat and rat: further studies on the anatomy of pain modulation.Journal of Comparative Neurology 187, 513–32.

    PubMed  Google Scholar 

  • Beaudet, A. &Sotelo, C. (1981) Synaptic remodelling of serotonin axon terminals in rat agranular cerebellum.Brain Research 206, 305–29.

    PubMed  Google Scholar 

  • Besson, J. M. &Chaouch, A. (1987) Peripheral and spinal mechanisms of nociception.Physiological Reviews 67, 67–186.

    PubMed  Google Scholar 

  • Brodal, A., Taber, E. &Walberg, F. (1960) The raphe nuclei of the brain stem in the cat. II. Efferent connections.Journal of Comparative Neurology 114, 239–59.

    Google Scholar 

  • Chan-Palay, V. (1975) Fine structure of labelled axons in the cerebellar cortex and nuclei of rodents and primates after intraventricular infusions with tritiated serotonin.Anatomy and Embryology 148, 235–65.

    PubMed  Google Scholar 

  • Coote, J. H. &Macleod, V. H. (1974) The influence of bulbospinal monoaminergic pathway on sympathetic nerve activity.Journal of Physiology 241, 453–75.

    PubMed  Google Scholar 

  • Dahlstrom, A. &Fuxe, K. (1964) Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brainstem neurons.Acta Physiologica Scandinavica 62, 1–55.

    Google Scholar 

  • Daval, G., Verge, D., Basbaum, A. I., Bourgoin, S. &Hamon, M. (1987) Autoradiographic evidence of serotonin 1 binding site on primary afferent fibres in the dorsal horn of the rat spinal cord.Neuroscience Letters 83, 71–6.

    PubMed  Google Scholar 

  • El-Yassir, N., Fleetwood-Walker, S. M. &Mitchell, R. (1988) Heterogeneous effects of serotonin in the dorsal horn of rat: the involvement of 5-HT1 receptor subtypes.Brain Research 456, 147–58.

    PubMed  Google Scholar 

  • Fasmer, O. B., Berge, O. G., Walther, B. &Hole, K. (1983) Changes in nociception after intrathecal administration of 5–6 dihydroxytryptamine in mice.Neuropharmacology 22, 1197–201.

    PubMed  Google Scholar 

  • Fields, H. L., Basbaum, A. I., Clanton, C. H. &Anderson, S. D. (1977) Nucleus raphe magnus inhibition of spinal cord dorsal horn neurons.Brain Research 126, 441–53.

    PubMed  Google Scholar 

  • Fischette, C. T., Nock, B. &Renner, K. (1987) Effects of 5,7-dihydroxytryptamine on serotonin-1 and serotonin-2 receptors throughout the rat central nervous system using quantitative autoradiography.Brain Research 421, 263–79.

    PubMed  Google Scholar 

  • Fung, S. J. &Barnes, C. D. (1989) Raphé-produced excitation of spinal cord motoneurones in the cat.Neuroscience Letters 103, 185–90.

    PubMed  Google Scholar 

  • Geffard, M., Henrick-Rock, A. M., Dulluc, J. &Seguela, P. (1985) Antisera against small neurotransmitter like molecules.Neurochemistry International 7, 403–13.

    Google Scholar 

  • Gilbey, M. P., Coote, J. H., Macleod, V. H. &Peterson, D. F. (1981) Inhibition of sympathetic activity by stimulation in the raphe nuclei and the role of 5-hydroxytryptamine in this effect.Brain Research 226, 131–42.

    PubMed  Google Scholar 

  • Glaum, S. R., Proudfit, H. K. &Anderson, E. G. (1988) Reversal of the antinociceptive effects of intrathecally administered serotonin in the rat by a selective 5-HT3 receptor antagonist.Neuroscience Letters 95, 313–17.

    PubMed  Google Scholar 

  • Glaum, S. R., Proudfit, H. K. &Anderson, E. G. (1990) 5-HT3 receptors modulate spinal nociceptive reflexes.Brain Research 510, 12–16.

    PubMed  Google Scholar 

  • Glazer, E. J. &Basbaum, A. I. (1984) Axons which take up [3H] serotonin are presynaptic to enkephalin immunoreactive neurons in cat dorsal horn.Brain Research 298, 386–91.

    PubMed  Google Scholar 

  • Gobel, S., Falls, W. M., Bennett, G. J., Abdelnoumene, M., Hayashi, H. &Humphrey, E. (1980) An EM analysis of the synaptic connections of horseradish peroxidasefilled stalked cells and islet cells in the substantia gelatinosa of adult cat spinal cord.Journal of Comparative Neurology 194, 781–807.

    PubMed  Google Scholar 

  • Hamon, M., Gallissot, M. C., Menard, F., Gozlan, H., Bourgoin, S. &Verge, D. (1989) 5-HT3 receptor binding sites are on capsaicin-sensitive fibres in the rat spinal cord.European Journal of Pharmacology 164, 315–22.

    PubMed  Google Scholar 

  • Hoffert, M. J., Miletic, V., Ruda, M. A. &Dubner, R. (1983) Immunocytochemical identification of serotonin axonal contacts on characterized neurons in laminae I and II of the cat dorsal horn.Brain Research 267, 361–4.

    PubMed  Google Scholar 

  • Hökfelt, T., Ljungdahl, A., Steinbusch, H., Verhofstad, A. N., Nilsson, G., Brodin, E., Pernow, B. &Goldstein, M. (1978) Immunohistochemical evidence of substance P-like immunoreactivity in some 5-hydroxytryptamine containing neurons in the rat central nervous system.Neuroscience 3, 517–38.

    PubMed  Google Scholar 

  • Howe, J. R. &Yaksh, T. L. (1982) Changes in sensitivity to intrathecal norepinephrine and serotonin after 6-hydroxydopamine (6-OHDA), 5,6-dihydroxytryptamine (5,6-DHT) or repeated monoamine administration.Journal of Pharmacology and Experimental Therapeutics 220, 311–21.

    PubMed  Google Scholar 

  • Hunt, S. P., Kelly, J. S., Emson, P. C., Kimmel, J. R., Miller, R. J. &Wu, J. Y. (1981) An immunohistochemical study of neuronal populations containing neuropeptides or gammaaminobutyrate within the superficial layers of the rat dorsal horn.Neuroscience 6, 1883–98.

    PubMed  Google Scholar 

  • Johansson, O., Hökfelt, T., Pernow, B., Jeffcoate, S. L., White, N., Steinbusch, H. W. M., Verhofstad, A. A. J., Emson, P. C. &Spindel, E. (1981) Immunohistochemical support for three putative transmitters in one neuron: coexistence of 5-hydroxytryptamine, substance P and thyrotropin releasing hormone-like immunoreactivity in medullary neurons projecting to the spinal cord.Neuroscience 6, 1857–81.

    PubMed  Google Scholar 

  • Light, A. R., Kavookjian, A. M. &Petrusz, P. (1983) The ultrastructure and synaptic connections of serotonin-immunoreactive terminals in spinal laminae I and II.Somatosensory Research 1, 33–50.

    PubMed  Google Scholar 

  • Marlier, L., Rajaofetra, N., Poulat, P. &Privat, A. (1990) Modification of serotonergic innervation of the rat spinal cord dorsal horn after neonatal capsaicin treatment.Journal of Neuroscience Research 25, 112–18.

    PubMed  Google Scholar 

  • Maxwell, D. J., Leranth, C. &Verhofstad, A. A. J. (1983) Fine structure of serotonin-containing axons in the marginal zone of the rat spinal cord.Brain Research 266, 253–9.

    PubMed  Google Scholar 

  • Miletic, V., Hoffert, M. J., Ruda, M. A., Dubner, R. &Shigenaga, Y. (1984) Serotonergic axonal contacts on identified cat spinal dorsal horn neurons and their correlation with nucleus raphe magnus stimulation.Journal of Comparative Neurology 228, 129–41.

    PubMed  Google Scholar 

  • Molander, C., Xu, Q. &Grant, G. (1984) The cytoarchitectonic organization of the spinal cord in the rat. I. The lower thoracic and lumbosacral cord.Journal of Comparative Neurology 230, 133–41.

    PubMed  Google Scholar 

  • Molander, C., Xu, Q., Riveromelian, C. &Grant, G. (1989) Cytoarchitectonic organization of the spinal cord in the rat. 2. The cervical and upper thoracic cord.Journal of Comparative Neurology 289, 375–85.

    PubMed  Google Scholar 

  • Monroe, P. J. &Smith, D. J. (1983) Characterization of multiple [3H]5-hydroxytryptamine binding sites in the rat spinal cord tissue.Journal of Neurochemistry 41, 349–55.

    PubMed  Google Scholar 

  • Newton, B. W., Maley, B. E. &Hamill, R. W. (1986) Immunohistochemical demonstration of serotonin neurons in the autonomic regions of the rat spinal cord.Brain Research 376, 155–63.

    PubMed  Google Scholar 

  • Nishikawa, N., Bennett, G. J., Ruda, M. A., Lu, G. W. &Dubner, R. (1983) Immunocytochemical evidence for a serotonergic innervation of dorsal column post-synaptic neurons in cat and monkey: light- and electron-microscopic observations.Neuroscience 10, 1333–40.

    PubMed  Google Scholar 

  • Pazos, A., Cortes, R. &Palacios, J. M. (1985) Quantitative autoradiographic mapping of serotonin receptors in the rat brain. II. Serotonin-2 receptors.Brain Research 346, 231–49.

    PubMed  Google Scholar 

  • Pazos, A. &Palacios, J. M. (1985) Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors.Brain Research 346, 205–30.

    PubMed  Google Scholar 

  • Pelletier, G., Steinbusch, H. W. M. &Verhofstad, A. A. J. (1981) Immunoreactive substance P and serotonin present in the same dense-core vesicles.Nature 293, 71–2.

    PubMed  Google Scholar 

  • Peters, A., Palay, S. L. &Webster, H. de F. (1970)The Fine Structure of the Nervous System. New York: Hoeber-Harper and Row.

    Google Scholar 

  • Privat, A., Mansour, H., Pavy, A., Geffard, M. &Sandillon, F. (1986) Transplantation of dissociated fetal serotonin neurons into the transected spinal cord of adult rats.Neuroscience Letters 66, 61–6.

    PubMed  Google Scholar 

  • Poulat, P., Marlier, L., Sandillon, F. &Privat, A. (1988) Light- and electron-microscope immunocytochemistry of 5-HT and substance P (SP) innervatin of the intermediolateral cell column on the rat spinal cord.Abstracts of the 11th Annual Meeting of the European Neuroscience Association, Zürich 4–8 September, p. 260.

  • Rajaofetra, N., Sandillon, F., Geffard, M. &Privat, A. (1989) Pre- and post-natal ontogeny of serotonergic projections to the rat spinal cord.Journal of Neuroscience Research 22, 305–21.

    PubMed  Google Scholar 

  • Rexed, B. (1952) The cytoarchitectonic organisation of the spinal cord in the cat.Journal of Comparative Neurology 96, 415–95.

    Google Scholar 

  • Rivot, J. P., Chaouch, A. &Besson, J. M. (1980) Nucleus raphe magnus modulation of response of rat dorsal horn neurons to unmyelinated fiber inputs: partial involvement of serotonergic pathways.Journal of Neurophysiology 44, 1039–57.

    PubMed  Google Scholar 

  • Roberts, M. H. T., Davies, M., Girdleston, D. &Foster, G. A. (1988) Effects of 5-hydroxytryptamine agonists and antagonists on the responses of rat spinal motoneurones to raphe obscurus stimulation.British Journal of Pharmacology 95, 437–48.

    PubMed  Google Scholar 

  • Ruda, M. A., Allen, B. &Gobel, S. (1981) Ultrastructural analysis of medial brain stem afferents to the spinal dorsal horn.Brain Research 205, 175–80.

    PubMed  Google Scholar 

  • Ruda, M. A., Coffield, J. &Steinbusch, H. W. M. (1982) Immuncytochemical analysis of serotononergic axons in laminae I and II of the lumbar spinal cord of the cat.Journal of Neuroscience 2, 1660–71.

    PubMed  Google Scholar 

  • Ruda, M. A. &Gobel, S. (1980) Ultrastructural characterization of axonal endings in the substantia gelatinosa which take up [3H]serotonin.Brain Research 184, 57–83.

    PubMed  Google Scholar 

  • Seguela, P., Watkins, K. C. &Descarries, L. (1989) Ultrastructural relationships of serotonin axon terminals in the cerebral cortex of the adult rat.Journal of Comparative Neurology 289, 129–42.

    PubMed  Google Scholar 

  • Skagerberg, G. &Björklund, A. (1985) Topographic principles in the spinal projections of serotonergic brainstem neurons in the rat.Neuroscience 15, 445–80.

    PubMed  Google Scholar 

  • Steinbusch, H. W. M. (1981) Distribution of serotonin immunoreactivity in the central nervous system of the rat; cell bodies and terminals.Neuroscience 6, 557–618.

    PubMed  Google Scholar 

  • Sternberger, L. A. (1979)Immunocytochemistry. New York: John Wiley & Sons.

    Google Scholar 

  • Tashiro, T., Satoda, T., Takahashi, O., Matsushima, R. &Mizuno, N. (1988) Distribution of axons exhibiting both enkephalin- and serotonin-like immunoreactivity in the lumbar cord segment: an immunohistochemical study in the cat.Brain Research 440, 357–62.

    PubMed  Google Scholar 

  • Willcockson, W. S., Chung, J. M., Hori, Y., Lee, K. H. &Willis, W. D. (1984) Effects of iontophoretically released amino acids and amines on primate spinothalamic tract cells.Journal of Neuroscience 4, 732–40.

    PubMed  Google Scholar 

  • Yaksh, T. L. &Wilson, P. R. (1979) Spinal serotonin terminal system mediates antinociception.Journal of Pharmacology and Experimental Therapeutics 208, 446–53.

    PubMed  Google Scholar 

  • Zemlan, F. P., Kow, L.-M. &Pfaff, D. W. (1983) Spinal serotonin (5-HT) receptor subtypes and nociception.Journal of Pharmacology and Experimental Therapeutics 226, 477–85.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Inserm U-336, U.S.T.L. CASE COURRIER, 106, Place Eugene Bataillon, 34095, Montpellier Cedex 05, France

    L. Marlier, F. Sandillon, P. Poulat, N. Rajaofetra & A. Privat

  2. CNRS Laboratory of Neuroimmunology, 33077, Bordeaux, France

    M. Geffard

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  1. L. Marlier
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  2. F. Sandillon
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  3. P. Poulat
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  4. N. Rajaofetra
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  5. M. Geffard
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  6. A. Privat
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Marlier, L., Sandillon, F., Poulat, P. et al. Serotonergic innervation of the dorsal horn of rat spinal cord: light and electron microscopic immunocytochemical study. J Neurocytol 20, 310–322 (1991). https://doi.org/10.1007/BF01235548

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  • DOI: https://doi.org/10.1007/BF01235548

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