Neurotransmitters and Neuropeptides: Distribution Patterns and Cellular Localization as Revealed by Immunocytochemistry

  • T. Hökfelt
  • O. Johansson
  • Å. Ljungdahl
  • J. Lundberg
  • M. Schultzberg
  • K. Fuxe
  • M. Goldstein
  • H. Steinbusch
  • A. Verhofstad
  • R. Elde
Part of the Published Nobel Symposia book series (NOFS, volume 42)


During the last years dramatic advances have been made with regard to the possibility to analyse the nervous system, not at least the hypothalamus, with histochemical methods. This is in part due to the fact that immunohistochemical techniques have been employed in the analysis and identification of specific neuron systems. The immunohistochemical approach is characterized by its unique general applicability, since principally any substance can be traced against which antibodies can be raised. Immunohisto-chemistry was originally introduced more than thirty years ago by Coons and collaborators (see 1). It was successfully applied to transmitter related problems by Geffen et al. (2) who identified catecholamine neurons with antibodies to dopamine-β-hydroxylase, the enzyme converting dopamine to noradrenaline. Now the phase has been reached where the full capacity of this technique can be exploited in studies on the nervous system. This is a consequence of the fact that only now have a larger number of enzymes and peptides been purified and structurally characterized in a way that they can be utilized as proper antigens for raising antisera.


Tyrosine Hydroxylase Thyrotropin Release Hormone External Layer Median Eminence Large Vesicle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Coons, A.H. In General Cytochemical Methods, pp. 399–422, Ed. Danielli, J.F., Academic Press, New York, 1958.Google Scholar
  2. 2.
    Geffen, L.B., Livett, B.G. and Rush, R.A. J. Physiol. (Lond.) 204, 593–605, 1969.Google Scholar
  3. 3.
    Nakane, P. In Karolinska Symposia on Research Methods in Repro-ductive Endocrinology Vol. 3, pp. 190–204, Ed. Piczfalusy, E., Forum, Copenhagen, 1971.Google Scholar
  4. 4.
    Sternberger, L.A. Immunocytochemistry. Prentice Hall, Engle-wood Cliffs, N.J., 1974.Google Scholar
  5. 5.
    Koelle, G.B. and Friedenwald, J.S. Proc. Soc. Exptl. Biol. Med. 70, 617–622, 1949.Google Scholar
  6. 6.
    Silver, A. The Biology of Cholinesterases. North Holland Publ. Comp., Oxford, Ams terdam, 1974.Google Scholar
  7. 7.
    Falck, B. Acta physiol. scand. 56, Suppl. 197, 1–25, 1962.Google Scholar
  8. 8.
    Falck, B., Hillarp, N.-A., Thieme, G. and Torp, A. J. Histo-chem. 10, 348–354, 1962.CrossRefGoogle Scholar
  9. 9.
    Carlsson, A., Falck, B. and Hillarp, N.-Å. Acta physiol. scand. 56, Suppl. 196, 1–28, 1962.Google Scholar
  10. 10.
    Hökfelt, T., Elde, R., Fuxe, K., Johansson, O., Ljungdahl, Å., Goldstein, M., Luft, R., Efendic, S., Nilsson, G., Terenius, L., Ganten, D., Jeffcoate, S., Rehfeld, J., Said, S., Perez de la Mora, M., Possani, L., Tapia, R., Teran, L. and Palacios, R. In The Hypothalamus, pp. 69–135, Ed. Reichlin, S., Baldessarini, R.J. and Martin, J.B., Raven Press, New York, 1978.Google Scholar
  11. 11.
    Elde, R. and Hökfelt, T. In Frontiers in Neuroendocrinology Vol. 5, pp. 1–33, Ed. Ganong, W.F. and Martini, L., Raven Press, New York, 1978.Google Scholar
  12. 12.
    Müller, E.E., Nistico, G. and Scapagnini, U. Neurotransmitter and Anterior Pituitary Function, Academic Press, New York, 1977.Google Scholar
  13. 13.
    Steinbusch, H., Verhofstad, A. and Joosten, H. Neuroscience, 1978, in press.Google Scholar
  14. 14.
    Fuxe, K. and Hökfelt, T. In Frontiers in Neuroendocrinology Vol. 1, pp. 47–96, Ed. Ganong, W.F. and Martini, L., Oxford University Press, New York, 1969.Google Scholar
  15. 15.
    Hökfelt, T. and Fuxe, K. In Brain-Endocrine Interaction. Median Eminence; Structure and Function, pp. 181–223, Ed. Knigge, K.M., Scott, D.E. and Weindl, A., Karger, Basel, 1972.Google Scholar
  16. 16.
    Björklund, A. and Nobin, A. Brain Res. 51, 193–205, 1973.PubMedCrossRefGoogle Scholar
  17. 17.
    Dahlström, A. and Fuxe, K. Acta physiol. scand. 62, Suppl. 232, 1–55, 1964.Google Scholar
  18. 18.
    Hökfelt, T., Johansson, O., Fuxe, K., Goldstein, M. and Park, D. Med. Biol. 54, 427–453, 1976.PubMedGoogle Scholar
  19. 19.
    Hökfelt, T., Johansson, O., Elde, R., Ljungdahl, Å., Fuxe, K. and Goldstein, M. In Cell Biology of Hypothalamic Neurosecretory Processes, Ed. Vincent, J.D. and Kordon, C., 1978, in press.Google Scholar
  20. 20.
    Sladek, J.R. Brain Res. 142, 165–173, 1978.PubMedCrossRefGoogle Scholar
  21. 21.
    Swanson, L.W. and Hartman, B. J. Comp. Neurol. 163, 467–505, 1975.CrossRefGoogle Scholar
  22. 22.
    Hökfelt, T., Fuxe, K., Goldstein, M. and Johansson, O. Brain Res. 66, 235–251, 1974.CrossRefGoogle Scholar
  23. 23.
    Brownstein, M.J., Palkovits, M., Tappaz, M.L., Saavedra, M. and Kizer, J.S. Brain Research 117, 287–295, 1976.PubMedCrossRefGoogle Scholar
  24. 24.
    Fuxe, K. Z. Zeilforsch. 65, 573–596, 1965.CrossRefGoogle Scholar
  25. 25.
    Fuxe, K. Acta physiol. scand. 64, Suppl. 247, 39–85, 1965.Google Scholar
  26. 26.
    Jonsson, G. Progr. Histochem. Cytochem. 2, 299–334, 1971.Google Scholar
  27. 27.
    Kordon, C., Javoy, F., Vassent, G. and Glowinski, J. Europ. J. Pharmacol. 4, 169–174, 1968.CrossRefGoogle Scholar
  28. 28.
    Saavedra, J.M., Palkovits, M., Brownstein, M. and Axelrod, J. Brain Res. 77, 157–165, 1974.PubMedCrossRefGoogle Scholar
  29. 29.
    Calas, A., Alonso, G., Arnauld, E. and Vincent, J.D. Nature 250, 241–243, 1974.PubMedCrossRefGoogle Scholar
  30. 30.
    Baumgarten, H.G. and Lachenmayer, L. Z. Zellforsch. 147, 285–292, 1974.PubMedCrossRefGoogle Scholar
  31. 31.
    Ajika, K. and Ochi, J. J. Anat., 1978, in press.Google Scholar
  32. 32.
    Sladek, J.R., Jr. and Sladek, C.D. Cell Tiss. Res. 186, 465–474, 1978.CrossRefGoogle Scholar
  33. 33.
    Hökfelt, T., Fuxe, K. and Goldstein, M. Brain Res. 62, 461–469, 1973.PubMedCrossRefGoogle Scholar
  34. 34.
    Lidbrink, P., Jonsson, G. and Fuxe, K. Brain Res. 67, 439–456, 1974.PubMedCrossRefGoogle Scholar
  35. 35.
    Chan-Palay, V. J. Comp. Neurol. 176, 467–494, 1977.CrossRefGoogle Scholar
  36. 36.
    Beaudet, A. and Descarries, L. Neurosci. Abst. 2, 479, 1976.Google Scholar
  37. 37.
    Smith, A.R. and Ariens Kappers, J.A. Brain Research 86, 353–371, 1975.PubMedCrossRefGoogle Scholar
  38. 38.
    Kent, D. and Sladek, J.R. Neurosci. Abst. 2, 493, 1976.Google Scholar
  39. 39.
    Hökfelt, T., Ljungdahl, Å., Steinbusch, H., Verhofstad, A., Nilsson, G., Brodin, E., Pernow, B. and Goldstein, M. Neuroscience 3, 517–538, 1978.PubMedCrossRefGoogle Scholar
  40. 40.
    Iversen, L. and Schon, F. In New Concepts in Transmitter Regulation, pp. 153–193, Ed. Mandel, A. and Segal, D., Plenum Press, New York, 1973.CrossRefGoogle Scholar
  41. 41.
    Hökfelt, T. and Ljungdahl, A. In The Use of Axonal Transport for Studies of Neuronal Connectivity, pp. 249–305, Ed. Cowan, W.M. and Cuénod, M., Elsevier, Amsterdam, 1974.Google Scholar
  42. 42.
    Roberts, E. In Neuroscience Symposia Vol. 1, pp. 123–138, Ed. Ferrendelli, J.A., McEwen, B.S. and Snyder, S.H., Society for Neuroscience, Bethesda, Md., 1975.Google Scholar
  43. 43.
    Livett, B.G., Uttenthal, L.O. and Hope, D.B. Proc. R. Soc. Phil. Trans. B. 261, 371–378, 1971.CrossRefGoogle Scholar
  44. 44.
    Zimmerman, E.A., Hsu, K.G., Robinson, A.G., Carmel, P.W., Frank, A.G. and Tannenbaum, M. Endocrinology 92, 931–940, 1973.PubMedCrossRefGoogle Scholar
  45. 45.
    Leonardelli, J., Barry, J. and Dubois, M.P. C.R. Acad. Sci. (D) (Paris) 276, 2043–2046, 1973.Google Scholar
  46. 46.
    Barry, J., Dubois, M.P. and Poulain, P. Z. Zellforsch. 146, 351–366, 1973.PubMedCrossRefGoogle Scholar
  47. 47.
    Calas, A., Kerdelhué, B., Assenmacher, I. and Jutisz, M. C.R. Acad. Sci. (D) (Paris) 277, 2765–2768, 1973.Google Scholar
  48. 48.
    Sternberger, L.A. and Hoffman, G.E. Neuroendocrinology 25, 111–128, 1978.PubMedCrossRefGoogle Scholar
  49. 49.
    Dyer, R.G. and Dyball, R.E.J. Nature 252, 486–488, 1974.PubMedCrossRefGoogle Scholar
  50. 50.
    Renaud, L.P., Martin, J.B. and Brazeau, P. Nature 255, 233–235, 1975.PubMedCrossRefGoogle Scholar
  51. 51.
    Otsuka, M. and Takahashi, T. Ann. Rev. Pharmacol. Toxicol. 17, 425–439, 1977.CrossRefGoogle Scholar
  52. 52.
    Watkins, W.B. Cell Tiss. Res. 155, 201–210, 1974.CrossRefGoogle Scholar
  53. 53.
    Silverman, A.J. and Zimmerman, E.A. Cell Tiss. Res. 159, 291–301, 1975.CrossRefGoogle Scholar
  54. 54.
    Dierickx, K., Vandesande, F. and DeMey, J. Cell Tiss. Res. 168, 141–151, 1976.CrossRefGoogle Scholar
  55. 55.
    Dube, D., Leclerc, R. and Pelletier, G. Am. J. Anat. 147, 103–108, 1976.PubMedCrossRefGoogle Scholar
  56. 56.
    Fuxe, K., Ganten, D., Hökfelt, T. and Bolme, P. Neurosci. Lett. 2, 229–234, 1976.PubMedCrossRefGoogle Scholar
  57. 57.
    Hökfelt, T., Pernow, B., Nilsson, G. Wetterberg, L., Goldstein, M. and Jeffcoate, S.L. Proc. Natl. Acad. Sci. USA 75, 1013–1015, 1978.PubMedCrossRefGoogle Scholar
  58. 58.
    Harris, G.H. Neural Control of the Pituitary Gland. Edward Arnold, London, 1955.Google Scholar
  59. 59.
    Agnati, L., Fuxe, K., Hökfelt, T., Goldstein, M., Jeffcoate, S.L. and Elde, P. J. Histochem. Cytochem. 25, 1222–1236, 1977.PubMedCrossRefGoogle Scholar
  60. 60.
    Ajika, K. and Hökfelt, T. Brain Res. 57, 97–117, 1972.CrossRefGoogle Scholar
  61. 61.
    Pelletier, G., Labrie, F. Arimura, A. and Schally, A.V. Am. J. Anat. 140, 445–450, 1974.PubMedCrossRefGoogle Scholar
  62. 62.
    Pearse, A.G.E. Z. Krebsforsch. 84, 1–18, 1975.CrossRefGoogle Scholar
  63. 63.
    Hökfelt, T., Elfvin, L.-G., Elde, R., Schultzberg, M., Goldstein, M. and Luft, R. Proc. Natl. Acad. Sci. USA 74, 3587–3591, 1977.PubMedCrossRefGoogle Scholar
  64. 64.
    Chan-Palay, V., Jonsson, G. and Palay, S.L. Proc. Natl. Acad. Sci. USA 75, 1582–1586, 1978.PubMedCrossRefGoogle Scholar
  65. 65.
    Hökfelt, T., Ljungdahl, Å., Steinbusch, H., Verhofstad, A., Nilsson, G., Pernow, B. and Goldstein, M. Neuroscience 3, 517–538, 1978.PubMedCrossRefGoogle Scholar
  66. 66.
    Goldstein, M., Fuxe, K. and Hökfelt, T. Pharmacol, Rev. 24, 293–309, 1972.Google Scholar
  67. 67.
    Schultzberg, M., Hökfelt, T., Terenius, L., Elfvin, L.-G., Lundberg, J.M., Brandt, J., Elde, R. and Goldstein, M. Neuro-science, 1979, in press.Google Scholar
  68. 68.
    Schultzberg, M., Lundberg, J.M., Hökfelt, T., Terenius, L., Brandt, J., Elde, R.P. and Goldstein, M. Neuroscience, 1978, in press.Google Scholar
  69. 69.
    Baumgarten, H.G., Björklund, A., Lachenmayer, L., Nobin, A. and Stenevi, U. Acta physiol. scand. Suppl. 373, 1971.Google Scholar
  70. 70.
    Baumgarten, H.G., Björklund, A., Lachenmayer, L. and Nobin, A. Acta physiol. scand. Suppl. 391, 1973.Google Scholar
  71. 71.
    Daly, J., Fuxe, K. and Jonsson, G. Brain Research. 49, 476–482, 1973.PubMedCrossRefGoogle Scholar
  72. 72.
    Daly, J., Faxe, K. and Jonsson, G. Res. Cómm. Ghem. Pathol. Pharmacol. 7, 175–187, 1974.Google Scholar
  73. 73.
    Euler, U.S. von and Gaddum, J.H. J. Physiol, (Lorid.) 72, 74–87, 1931.Google Scholar
  74. 74.
    Hökfelt, T. Z. Zellforsch. 91, 1–74, 1968.PubMedCrossRefGoogle Scholar
  75. 75.
    Tranzer, J.-P., Thoenen, H., Snipes, R.L. and Richards, J. G. Progr. Brain Res, 31, 33–46, 1969.CrossRefGoogle Scholar
  76. 76.
    Chan-Palay, V. and Palay, S.L. Proc. Natl. Acad. Sci. USA 74, 4050–4054, 1977.PubMedCrossRefGoogle Scholar
  77. 77.
    Hökfelt, T., Johansson, O., Kellerth, J.-O., Ljungdahl, Å., Nilsson, G., Nygårds, A. and Pernow, B. In Substance P Nobel Symposium 37, pp. 117–145, Ed. Euler, U.S. von and Pernow, B., Raven Press, New York, 1977.Google Scholar
  78. 78.
    Pickel, V.M., Reis, D.J. and Leeman, S.E. Brain Res. 122, 534–540, 1977.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1979

Authors and Affiliations

  • T. Hökfelt
    • 1
  • O. Johansson
    • 1
  • Å. Ljungdahl
    • 1
  • J. Lundberg
    • 1
  • M. Schultzberg
    • 1
  • K. Fuxe
    • 1
  • M. Goldstein
    • 2
  • H. Steinbusch
    • 3
  • A. Verhofstad
    • 3
  • R. Elde
    • 4
  1. 1.Dept. of HistologyKarolinska InstituteStockholmSweden
  2. 2.Dept. of PsychiatryNew York University Medical CenterNew YorkUSA
  3. 3.Dept. of Anatomy and EmbryologyKatholieke UniversiteitNijmegenThe Netherlands
  4. 4.Dept. of AnatomyUniversity of MinnesotaMinneapolisUSA

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