Experimental Brain Research

, Volume 73, Issue 1, pp 69–77 | Cite as

Projections from the ventral tegmental area and mesencephalic raphe to the dorsal raphe nucleus in the rat

Evidence for a minor dopaminergic component
  • P. Kalén
  • G. Skagerberg
  • O. Lindvall
Article

Summary

The origins of the dopaminergic innervation of the rat dorsal raphe nucleus (NRD) have been investigated using a combination of fluorescent retrograde tracing and fluorescence histochemistry. Stereotaxic microinjections of True Blue were placed in the central, caudal and lateral portions of the NRD, and after 6–12 days survival the brains were processed for fluorescence histochemical detection of catecholamines. Retrogradely labeled neurons were searched for in the diencephalic A11 and A13 dopaminergic cell groups, substantia nigra, ventral tegmental area (VTA) and the linear, central superior and dorsal raphe nuclei. The various NRD injections consistently resulted in retrograde labeling of a small number of catecholamine-containing, presumed dopaminergic cell bodies, confined mainly to three regions: the VTA, the linear and central superior raphe nuclei and the NRD itself. The present findings indicate that not only dopaminergic neurons in the VTA but also the system of catecholamine-containing cells, extending dorsally and caudally from the VTA within the midline raphe area, project to the NRD. Although often similar in size, shape and distribution to the catecholaminergic neurons the majority of retrogradely labeled cells in these regions were, however, found to be non-catecholaminergic.

Key words

Catecholamine Dopamine Dorsal raphe nucleus Retrograde tracer Ventral tegmental area 

Abbreviations

3

Principal oculomotor nucleus

4

Trochlear nucleus

Aq

Cerebral aqueduct

cp

cerebral peduncle

cst

cortico-spinal tract

dscp

decussation of the superior cerebellar peduncle

DTg

Dorsal tegmental nucleus

fr

fasciculus retroflexus

IF

Interfascicular nucleus

IP

Interpeduncular nucleus

LL

nucleus of the lateral lemniscus

ml

medial lemniscus

mlf

medial longitudinal fasciculus

mNV

mesencephalic trigeminal nucleus

NLC

Nucleus linearis caudalis

NLR

Nucleus linearis rostralis

NRD

Dorsal raphe nucleus

PAG

Periaqueductal grey

PN

Pontine nucleus

PRN

Pontine raphe nucleus

R

Red nucleus

RCS

Nucleus raphe centralis superior

SN

Substantia nigra

VTA

Ventral tegmental area

VTg

Ventral tegmental nucleus

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abercrombie M (1946) Estimation of nuclear population from microtome sections. Anat Rec 94: 239–247Google Scholar
  2. Aghajanian GK, Wang RY (1977) Habenular and other midbrain raphe afferents demonstrated by a modified retrograde tracing technique. Brain Res 122: 229–242Google Scholar
  3. Beckstead RM, Domesick VB, Nauta WJH (1979) Efferent connections of the substantia nigra and ventral tegmental area in the rat. Brain Res 175: 191–217Google Scholar
  4. Björklund A, Lindvall O (1984) Dopamine-containing systems in the CNS. In: Björklund A, Hökfelt T (eds) Handbook of chemical neuroanatomy, Vol 2. Classical transmitters in the CNS, Part 1. Elsevier, Amsterdam New York, pp 55–122Google Scholar
  5. Björklund A, Skagerberg G (1979) Simultaneous use of retrograde fluorescent tracers and fluorescence histochemistry for convenient and precise mapping of monoaminergic projections and collateral arrangements in the CNS. J Neurosci Methods 1: 261–277Google Scholar
  6. Bobillier P, Seguin S, Dequeurce A, Lewis BD, Pujol J-F (1979) The efferent connections of the nucleus raphe centralis superior in the rat as revealed by radioautography. Brain Res 166: 1–8Google Scholar
  7. Bouthenet M-L, Martres M-P, Sales N, Schwartz J-C (1987) A detailed mapping of dopamine D-2 receptors in rat central nervous system by autoradiography with [125I] iodosulpride. Neuroscience 20: 117–155Google Scholar
  8. Dahlström 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 brain stem neurons. Acta Physiol Scand [Suppl 232] 62: 1–55Google Scholar
  9. Dawson TM, Gehlert DR, Tyler McCabe R, Barnett A, Wamsley JK (1986) D-1 dopamine receptors in the rat brain: a quantitative autoradiographic analysis. J Neurosci 6: 2352–2365Google Scholar
  10. Descarries L, Berthelet F, Garcia S, Beaudet A (1986) Dopaminergic projection from nucleus raphe dorsalis to neostriatum in the rat. J Comp Neurol 249: 511–520Google Scholar
  11. Hökfelt T, Johansson O, Goldstein M (1984) Central catecholamine neurons as revealed by immunohistochemistry with special reference to adrenaline neurons. In: Björklund A, Hökfelt T (eds) Handbook of chemical neuroanatomy, Vol 2. Classical transmitters in the CNS, Part I. Elsevier, Amsterdam New York, pp 157–276Google Scholar
  12. Hökfelt T, Johansson O, Fuxe K, Goldstein M, Park D (1976) Immunohistochemical studies on the localization and distribution of monoamine neuron systems in the rat brain. I. Tyrosine hydroxylase in mes- and diencephalon. Med Biol 54: 427–453Google Scholar
  13. Kalén P, Karlson M, Wiklund L (1985) Possible excitatory amino acid afferents to nucleus raphe dorsalis of the rat investigated with retrograde wheat germ agglutinin and D-[3H] aspartate tracing. Brain Res 360: 285–297Google Scholar
  14. Köhler C, Goldstein M (1984) Golgi-like immunoperoxidase staining of dopamine neurons in the reticular formation of the rat brainstem using antibody to tyrosine-hydroxylase. J Comp Neurol 223: 202–211Google Scholar
  15. Lee EHY, Geyer MA (1982) Selective effects of apomorphine on dorsal raphe neurons: a cytofluorimetric study. Brain Res Bull 9: 719–725Google Scholar
  16. Levitt P, Moore RY (1979) Origin and organization of brainstem catecholamine innervation in the rat. J Comp Neurol 186: 505–528Google Scholar
  17. Lindvall O, Björklund A (1974) The organization of the ascending catecholamine neuron systems in the rat brain as revealed by the glyoxylic acid fluorescence method. Acta Physiol Scand [Suppl] 412: 1–48Google Scholar
  18. Lorén I, Björklund A, Falck B, Lindvall O (1980) The aluminumformaldehyde (ALFA) histofluorescence method for improved visualization of catecholamines and indoleamines. I. A detailed account of the methodology for central nervous tissue using paraffin, cryostat or vibratome sections. J Neurosci Methods 2: 277–300Google Scholar
  19. Loughlin SE, Fallon JH (1983) Dopaminergic and non-dopaminergic projections to amygdala from substantia nigra and ventral tegmental area. Brain Res 262: 334–338Google Scholar
  20. Marchand JE, Hagino N (1983) Afferents to the periaqueductal gray in the rat. A horseradish peroxidase study. Neuroscience 9: 95–106Google Scholar
  21. Mosko SS, Haubrich D, Jacobs BL (1977) Serotonergic afferents to the dorsal raphe nucleus: evidence from HRP and synaptosomal uptake studies. Brain Res 119: 269–290Google Scholar
  22. Nagatsu I, Inagaki S, Kondo Y, Karasawa N, Nagatsu T (1979) Immunofluorescent studies on the localization of tyrosine hydroxylase and dopamine-β-hydroxylase in the mes-, di-, and telencephalon of the rat using unperfused fresh frozen sections. Acta Histochem Cytochem 12: 20–37Google Scholar
  23. Ochi J, Shimizu K (1978) Occurrence of dopamine-containing neurons in the midbrain raphe nuclei of the rat. Neurosci Lett 8: 317–320Google Scholar
  24. Ornstein K, Milon H, McRae-Degueurce A, Alvarez C, Berger B, Wurzner HP (1987) Biochemical and radioautographic evidence for dopaminergic afferents of the locus coeruleus originating in the ventral tegmental area. J Neural Transm 70: 183–193Google Scholar
  25. Palacios JM, Wamsley JK (1984) Catecholamine receptors. In: Björklund A, Hökfelt T, Kuhar MJ (eds) Handbook of chemical neuroanatomy, Vol 3. Classical transmitters and transmitter receptors in the CNS, Part II. Elsevier, Amsterdam New York, pp 325–351Google Scholar
  26. Pasquier DA, Kemper TL, Forbes WB, Morgane PJ (1977) Dorsal raphe, substantia nigra and locus coeruleus: interconnections with each other and the neostriatum. Brain Res Bull 2: 323–339Google Scholar
  27. Paxinos G, Watson C (1982) The rat brain in stereotaxic coordinates. Academic Press, SydneyGoogle Scholar
  28. Ramm P, Beninger RJ, Frost BJ (1984) Functional activity in the lateral habenular and dorsal raphe nuclei following administration of several dopamine receptor antagonists. Can J Physiol Pharmacol 62: 1530–1533Google Scholar
  29. Sakai K, Salverg D, Touret M, Jouvet M (1977) Afferent connections of the nucleus raphe dorsalis in the cat as visualized by the horseradish peroxidase technique. Brain Res 137: 11–35Google Scholar
  30. Simon H, Le Moal M, Calas A (1979) Efferents and afferents of the ventral tegmental-A10 region studied after local injection of [3H] leucine and horseradish peroxidase. Brain Res 178: 17–40Google Scholar
  31. Skagerberg G, Lindvall O, Björklund A (1984) Origin, course and termination of the mesohabenular dopamine pathway in the rat. Brain Res 307: 99–108Google Scholar
  32. Skagerberg G, Björklund A, Lindvall O (1985) Further studies on the use of the fluorescent retrograde tracer true blue in combination with monoamine histochemistry. J Neurosci Methods 14: 25–40Google Scholar
  33. Skagerberg G, Meister B, Hökfelt T, Lindvall O, Goldstein M, Joh T, Cuello AC (1988) Studies on dopamine-, tyrosine hydroxylase and aromatic L-amino acid decarboxylase-containing cells in the rat diencephalon: comparison between formaldehyde-induced histofluorescence and immunofluorescence. Neuroscience 24: 605–620Google Scholar
  34. Soubrié P, Reisine TD, Glowinski J (1984) Functional aspects of serotonin transmission in the basal ganglia: a review and an in vivo approach using the push-pull cannula technique. Neuroscience 13: 605–625Google Scholar
  35. Steinbusch HWM, Nieuwenhuys R (1983) The raphe nuclei of the rat brainstem: a cytoarchitectonic and immunohistochemical study. In: Emson PC (ed) Chemical neuroanatomy. Raven Press, New York, pp 131–207Google Scholar
  36. Swanson LW(1982) The projections of the ventral tegmental area and adjacent regions: a combined fluorescent retrograde tracer and immunofluorescence study in the rat. Brain Res Bull 9: 321–353Google Scholar
  37. Trulson ME, Cannon MS, Raese JD (1985) Identification of dopamine-containing cell bodies in the dorsal and median raphe nuclei of the rat brain using tyrosine hydroxylase immunocytochemistry. Brain Res Bull 15: 229–234Google Scholar
  38. Versteeg DHG, Van der Gugten J, De Jong W, Palkovits M (1976) Regional concentrations of noradrenaline and dopamine in rat brain. Brain Res 113: 563–574Google Scholar
  39. Vogt M (1982) Some functional aspects of central serotonergic neurones. In: Osborne NN (ed) Biology of serotonergic transmission. Wiley, New York, pp 299–315Google Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • P. Kalén
    • 1
  • G. Skagerberg
    • 1
  • O. Lindvall
    • 1
  1. 1.Department of Medical Cell ResearchUniversity of LundLundSweden

Personalised recommendations