Skip to main content
Log in

Late prenatal ontogeny of central monoamine neurons in the rat: Fluorescence histochemical observations

  • Published:
Zeitschrift für Anatomie und Entwicklungsgeschichte Aims and scope Submit manuscript

Summary

The development of all monoamine-containing neuron systems in the rat brain throughout the last seven days of gestation, i.e. from the 15th day to term, crown rump length (CRL) 16 mm to 42 mm, has been followed using the Falck-Hillarp method for fluorescence histochemistry. Serial sagittal, horizontal and transverse sections through whole brains of fetuses from MAO-inhibited mothers have been carefully analyzed by fluorescence microscopy, and drawings of almost all sections depicting specific fluorescence have been collected from 10 of the 16 analyzed brains. Thus, all the 5-hydroxytryptamine (5-HT), dopamine (DA) and noradrenaline (NA) neuron systems have been mapped, both regarding the cell groups, the formation of axon pathways and the development of terminal plexuses in the whole brain prenatally. Together with a previous report (Olson and Seiger, 1972a) the present data have made it possible to determine the common origin of groups A1–A3, A4–A7, A8–A10, B1–B3 and B4–B9, respectively (nomenclature according to Dahlström and Fuxe, 1964). These findings and an estimation of the number of visible fluorescent cells in all monoamine cell complexes throughout the prenatal period of development have been summarized in a flow-chart. In the full-term fetus all monoamine neurons and their axon pathways, except for the hypothalamic cell groups, are very well developed. Thus, the new neuroanatomical data presented, in all probability hold true also for the adult state. A comprehension of the innervation course of neostriatum by DA nerve terminals from the 14th day of gestation to adult hood is given.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Amano, T., Richelson, E., Nirenberg, M.: Neurotransmitter synthesis by neuroblastoma clones. Proc. nat. Acad. Sci. (Wash.) 69, 258–263 (1972).

    Google Scholar 

  • Andén, N.-E., Dahlström, A., Fuxe, K., Larsson, K., Olson, L., Ungerstedt, U.: Ascending monoamine neurons to the telencephalon and diencephalon. Acta physiol. scand. 67, 313–326 (1966).

    Google Scholar 

  • Bartels, W.: Die Ontogenese der aminhaltigen Neuronensysteme im Gehirn von Rana temporaria. Z. Zellforsch. 116, 94–118 (1971).

    Google Scholar 

  • Bazelon, M., Paine, R. S., Cowie, V. A., Hunt, P., Houck, J. C., Mahanand, D.: Reversal of hypotonia in infants with Down's syndrome by administration of 5-hydroxytryptophan. Lancet 1967I, 1130.

  • Björklund, A., Enemar, A., Falck, B.:Monoamines in the hypothalamo-hypophyseal system of the mouse with special reference to the ontogenetic aspects. Z. Zellforsch. 89, 590–607 (1968).

    Google Scholar 

  • Breese, G. R., Traylor, T. D.: Developmental characteristics of brain catecholamines and tyrosine hydroxylase in the rat: effects of 6-hydroxydopamine. Brit. J. Pharmacol. 44, 210–222 (1972).

    Google Scholar 

  • Buznikov, G. A., Chudakova, I. V., Berdycheva, L. V., Vyazmina, N. M.: The role of neuro-humors in early embryogenesis. II. Acetylcholine and catecholamine content in developing embryos of sea urchin. J. Embryol. exp. Morph. 20, 119–128 (1968).

    Google Scholar 

  • Buznikov, G. A., Kost, A. N., Kucherova, N. F., Mndzhoyan, A. L., Suvorov, N. N., Berdycheva, L. V.: The role of neurohumours in early embryogenesis. III. Pharmacological analysis of the role of neurohumours in cleavage divisions. J. Embryol. exp. Morph. 23, 549–569 (1970).

    Google Scholar 

  • Corrodi, H., Jonsson, G.: The formaldehyde fluorescence method for the histochemical demonstration of biogenic amines. A review on the methodology. J. Histochem. Cytochem. 15, 65–78 (1967).

    Google Scholar 

  • Coyle, J. T., Axelrod, J.: Development of the uptake and storage of L-(3H) norepinephrine in the rat brain. J. Neurochem. 18, 2061–2075 (1971).

    Google Scholar 

  • Coyle, J. T., Axelrod, J.: Dopamine-β-hydroxylase in the rat brain: developmental characteristics. J. Neurochem. 19, 449–459 (1972a).

    Google Scholar 

  • Coyle, J. T., Axelrod, J.: Tyrosine hydroxylase in rat brain: developmental characteristics. J. Neurochem. 19, 1117–1123 (1972b).

    Google Scholar 

  • Dahlström, A., Fuxe, K.: Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta physiol. scand. 62, Suppl. 232, 1–55 (1964).

    Google Scholar 

  • Dahlström, A., Fuxe, K.: Evidence for the existence of monoamine-containing neurons in the central nervous system. II. Experimentally induced changes in the intraneuronal amine levels of bulbospinal neuron systems. Acta physiol. scand. 64, Suppl. 247, 1–36 (1965).

    Google Scholar 

  • Das, G. D., Hine, R. J.: Nature and significance of spontaneous degeneration of axons in the pyramidal tract. Z. Anat. Entwickl.-Gesch. 136, 98–114 (1972).

    Google Scholar 

  • Falck, B., Hillarp, N.-Å., Thieme, G., Torp, A.: Fluorescence of catechol amines and related compounds condensed with formaldehyde. J. Histochem. Cytochem. 10, 348–354 (1962).

    Google Scholar 

  • Fuxe, K.: Evidence for the existence of monoamine-containing neurons in the central nervous system. III. The monoamine nerve terminal. Z. Zellforsch. 65, 573–596 (1965a).

    Google Scholar 

  • Fuxe, K.: Evidence for the existence of monoamine-containing neurons in the central nervous system. IV. Distribution of monoamine nerve terminals in the central nervous system. Acta physiol. scand. 64, Suppl. 247, 39–85 (1965b).

    Google Scholar 

  • Fuxe, K., Hökfelt, T., Olson, L., Ungerstedt, U.: Central monoaminergic pathways with emphasis on their relation to the so called “extrapyramidal motor system”. In: The pharmacology of the extrapyramidal system (O. Hornykiewicz ed.). International encyclopedia of pharmacology and therapeutics. Pergamon Press. Oxford 1973 (in press).

    Google Scholar 

  • Golden, G. S.: Embryologic demonstration of a nigro-striatal projection in the mouse. Brain Res. 44, 278–282 (1972).

    Google Scholar 

  • Golden, G. S., Comme-de Broth, R.: Ontogenesis of the substantia nigra of the mouse. Trans. 24th Ann. Meet. Amer. Acad. Neurol., St. Louis, April 1972.

  • Hanaway, J., McConnell, J. A., Netsky, M. G.: Histogenesis of the substantia nigra, ventral tegmental area of Tsai and interpeduncular nucleus: An autoradiographic study in the mesencephalon in the rat. J. comp. Neurol. 142, 59–74 (1971).

    Google Scholar 

  • Harrison, R. G.: The Croonian lecture. On the origin and development of the nervous system studied by the methods of experimental embryology. Proc. roy. Soc. B 118, 155–196 (1935).

    Google Scholar 

  • Hyyppä, M.: A histochemical study of the primary catecholamines in the hypothalamic neurons of the rat in relation to the ontogenetic and sexual differentiation. Z. Zellforsch. 98, 550–560 (1969).

    Google Scholar 

  • Hyyppä, M.: Hypothalamic monoamines in human fetuses. Neuroendocrinology 9, 257–266 (1972).

    Google Scholar 

  • Ifft, J. D.: An autoradiographic study of the time of final division of neurons in rat hypothalamic nuclei. J. comp. Neurol. 144, 193–204 (1972).

    Google Scholar 

  • Ignarro, L. J., Shideman, F. E.: Norepinephrine and epinephrine in the embryonic heart of the chick: uptake and subcellular distribution. J. Pharmacol. exp. Ther. 159, 49–58 (1968).

    Google Scholar 

  • Jonsson, G.: Quantitation of fluorescence of biogenic monoamines. Progr. Histochem. Cytochem. 2, 299–334 (1971).

    Google Scholar 

  • Kellogg, C., Lundborg, P.: Production of (3H) catecholamines in the brain following the peripheral administration of 3H-dopa during pre- and postnatal development. Brain Res. 36, 333–342 (1972).

    Google Scholar 

  • Kirby, M. L., Gilmore, S. A.: A fluorescence study on the ability of the notochord to synthesize and store catecholamines in early chick embryos. Anat. Rec. 173, 469–478 (1972).

    Google Scholar 

  • Loizou, L.: The development of monoamine-containing neurones in the brain of the albino rat. J. Anat. (Lond.) 104, 588 (1969).

    Google Scholar 

  • Loizou, L.: Uptake of monoamines into central neurones and the blood-brain barrier in the infant rat. Brit. J. Pharmacol. 40, 800–813 (1970).

    Google Scholar 

  • Loizou, L.: The postnatal development of monoamine-containing structures in the hypothalamo-hypophyseal system of the albino rat. Z. Zellforsch. 114, 234–252 (1971a).

    Google Scholar 

  • Loizou, L.: Effect of inhibition of catecholamine synthesis on central catecholamine-containing neurones in the developing albino rat. Brit. J. Pharmacol. 41, 41–48 (1971b).

    Google Scholar 

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

    Google Scholar 

  • Loup, M., Cadilhac, J.: Le développement des neurones à monoamines du cerveau chez le chaton. C. R. Soc. Biol. (Paris) 164, 1582–1587 (1970).

    Google Scholar 

  • Lundborg, P., Kellogg, C.: Formation of (3H) noradrenaline and (3H) dopamine in the brain and heart of the rat foetus. Brain Res. 29, 387–389 (1971).

    Google Scholar 

  • Maeda, T., Shimizu, N.: Projections ascendantes du locus coeruleus et d'autres neurones aminergiques pontiques au niveau du prosencéphale du rat. Brain Res. 36, 19–35 (1972).

    Google Scholar 

  • Marin-Padilla, M.: Early prenatal ontogenesis of the cerebral cortex (neocortex) of the cat (Felis Domestica). A golgi study. I. The primordial neocortical organization. Z. Anat. Entwickl.-Gesch. 134, 117–145 (1971).

    Google Scholar 

  • Narayanan, C. H., Fox, M. W., Hamburger, V.: Prenatal development of spontaneous and evoked activity in the rat (rattus norvegicus albinus). Behaviour 40, 100–134 (1971).

    Google Scholar 

  • Nygren, L.-G., Olson, L., Seiger, Å.: Regeneration of monoamine-containing axons in the developing and adult spinal cord of the rat following intraspinal 6-OH-dopamine injections or transections. Histochemie 28, 1–15 (1971).

    Google Scholar 

  • Olson, L., Boréus, L. O., Seiger, Å.: Histochemical demonstration and mapping of 5-hydroxytryptamine- and catecholamine-containing neuron systems in the human fetal brain. Z. Anat. Entwickl.-Gesch. 139, 259–282 (1973).

    Google Scholar 

  • Olson, L., Fuxe, K.: On the projections from the locus coeruleus noradrenaline neurons: The cerebellar innervation. Brain Res. 28, 165–171 (1971).

    Google Scholar 

  • Olson, L., Fuxe, K.: Further mapping out of central noradrenaline neuron systems: Projections of the “subcoeruleus” area. Brain Res. 43, 289–295 (1972).

    Google Scholar 

  • Olson, L., Seiger, Å.: Early prenatal ontogeny of central monoamine neurons in the rat: Fluorescence histochemical observations. Z. Anat. Entwickl.-Gesch. 137, 301–316 (1972a).

    Google Scholar 

  • Olson, L., Seiger, Å.: Brain tissue transplanted to the anterior chamber of the eye. I. Fluorescence histochemistry of immature catecholamine and 5-hydroxytryptamine neurons reinnervating the rat iris. Z. Zellforsch. 135, 175–194 (1972b).

    Google Scholar 

  • Olson, L., Seiger, Å., Fuxe, K.: Heterogeneity of striatal and limbic dopamine innervation: Highly fluorescent islands in developing and adult rats. Brain Res. 44, 283–288 (1972).

    Google Scholar 

  • Olson, L., Ungerstedt, U.: A simple high capacity freeze-drier for histochemical use. Histochemie 22, 8–19 (1970).

    Google Scholar 

  • Pare, C. M. B., Sandler, M., Stacey, R. S.: 5-hydroxytryptamine deficiency in phenylketonuria. Lancet 1957I, 551.

  • Rugh, R.: The mouse: its reproduction and development. Minneapolis: Burgess Publishing Company 1968.

    Google Scholar 

  • Sachs, Ch., Jonsson, G., Fuxe, K.: Mapping of central noradrenaline pathways with 6-hydroxydopa. Brain Res. 1973 (in press)

  • Scheibel, M. E., Scheibel, A. B.: Anatomical basis of attention mechanisms in vertebrate brains. In: The neurosciences. A study program (G. C. Quarton, T. Melnechuk, and F. O. Schmitt, eds.), p. 577–602. New York: The Rockefeller University Press 1967.

    Google Scholar 

  • Schumann, H.: Vergleichende Untersuchungen über das Wachstum von Ratten-und Mäusenembryonen. Wilhelm Roux' Archiv 163, 325–333 (1969).

    Google Scholar 

  • Smith, G. C., Simpson, R. W.: Monoamine fluorescence in the median eminence of foetal, neonatal and adult rats. Z. Zellforsch. 104, 541–556 (1970).

    Google Scholar 

  • Taber, E.: Histogenesis of brain stem neurons studied autoradiographically with thymidine-H3 in the mouse. Anat. Rec. 148, 344 (1964).

    Google Scholar 

  • Taber-Pierce, E.: Histogenesis of the nuclei griseum pontis, corporis pontobulbaris and reticularis tegmenti pontis (Bechterew) in the mouse. An autoradiographic study. J. comp. Neurol. 126, 219–240 (1966).

    Google Scholar 

  • Tennyson, V. M., Barrett, R. E., Cohen, G., Côté, L., Heikkila, R., Mytilineou, C.: The developing neostriatum of the rabbit: correlation of fluorescence histochemistry, electron microscopy, endogenous dopamine levels, and (3H) dopamine uptake. Brain Res. 46, 251–287 (1972).

    Google Scholar 

  • Tu, J., Partington, M. W.: 5-hydroxyindole levels in the blood and CSF in Down's syndrome, phenylketonuria and severe mental retardation. Develop. Med. Child Neurol. 14, 457–466 (1972).

    Google Scholar 

  • Ungerstedt, U.: Stereotaxic mapping of the monoamine pathways in the rat brain. Acta physiol. scand., Suppl. 367, 1–48 (1971).

    Google Scholar 

  • Weiss, P.: Nerve patterns: The mechanics of nerve growth. Growth 5, 163–203 (1941).

    Google Scholar 

  • Weiss, P.: Nervous System (neurogenesis). In: Analysis of development (B. H. Willier, P. A. Weiss, and V. Hamburger, eds.), p. 346–401. Philadelphia-London: W. B. Saunders 1955.

    Google Scholar 

  • Windle, W. F., Baxter R. E.: Development of reflex mechanisms in the spinal cord of albino rat embryos. J. comp. Neurol. 63, 189–209 (195).

    Google Scholar 

  • Yamafuji, K., Murakami, H., Shinozuka, M.: Antitumour activity of Dopa, dopamine, noradrenalin or adrenalin and their reaction with nucleic acids. Z. Krebsforsch. 73, 195–203 (1970).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Seiger, Å., Olson, L. Late prenatal ontogeny of central monoamine neurons in the rat: Fluorescence histochemical observations. Z. Anat. Entwickl. Gesch. 140, 281–318 (1973). https://doi.org/10.1007/BF00525058

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00525058

Key words

Navigation