Neuroanatomy pp 449-475 | Cite as

Efferent Connections of the Substantia Nigra and Ventral Tegmental Area in the Rat

  • Robert M. Beckstead
  • Valerie B. Domesick
  • Walle J. H. Nauta
Part of the Contemporary Neuroscientists book series (CN)


Small injections of tritiated leucine and proline confined to the ventral tegmental area (AVT) were found to label fibers ascending: (a) to the entire ventromedial half of the striatum, but most massively to the ventral striatal zone that includes the nucleus accumbens; (b) to the thalamus: lateral habenular nucleus, nuclei reuniens and centralis médius, and the most medial zone of the mediodorsal nucleus; (c) to the posterior hypothalamic nucleus and possibly the lateral hypothalamic and preoptic region; (d) to the nuclei amygdalae centralis, lateralis and medialis; (e) to the bed nucleus of the stria terminalis, the nucleus of the diagonal band, and the medial half of the lateral septal nucleus; (f) to the anteromedial (frontocingulate) cortex; and (g) to the entorhinal area. Further AVT efferents descend to the medial half of the midbrain tegmentum including an anterior region of the median raphe nucleus, to the ventral half of the central grey substance including the dorsal raphe nucleus, to the parabrachial nuclei, and to the locus coeruleus.

Similar injections centered in the pars compacta of the substantia nigra (SNC) label fibers that are distributed in the striatum in an orderly medial-to-lateral arrangement, and almost entirely avoid the nucleus accumbens and olfactory tubercle. With the exception of the lateral quarter of the substantia nigra, which apparently does not project to the extreme rostral pole of the striatum, each small SNC locus, regardless of its anteroposterior localization, distributes nigrostriatal fibers throughout the length of the striatum. Descending SNC efferents are distributed to the same general regions that receive descending AVT projections, except that no SNC fibers appear to enter the locus coeruleus.

Isotope injections confined to the pars reticulata (SNR) label sparse nigrostriatal fibers, and numerous nigrothalamic fibers ascending mainly to the nucleus ventro-medialis and in lesser number to the parafascicular nucleus and the paralamellar zone of the nucleus mediodorsalis. Descending SNR fibers leave the nigra as a voluminous fiber bundle that bifurcates into a large nigrotectal and a smaller nigrotegmental component, the latter terminating largely in the pedunculopontine nucleus of the pontomesencephalic tegmentum.


Substantia Nigra Nucleus Accumbens Ventral Tegmental Area Locus Coeruleus Dorsal Raphe Nucleus 
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  1. 1.
    Afifi, A. K. and Kaelber, W. W., Efferent connections of the substantia nigra in the cat, Exp. Neurol., 11 (1965)474–482.CrossRefGoogle Scholar
  2. 2.
    Ahlenius, S., Potentiation by haloperidol of the catalepsy produced by lesions in the parafascicular nucleus of the rat, Brain Research, 150 (1978) 648–652.CrossRefGoogle Scholar
  3. 3.
    Andén, N.-E., Carlsson, A., Dahlström, A., Fuxe, K., Hillarp, N. A. and Larsson, K., Demonstration and mapping out of nigro-neostriatal dopamine neurons, Life Sei., 3 (1964) 523–530.CrossRefGoogle Scholar
  4. 4.
    Andén, N.-E., Dahlström, A., Fuxe, K., Larsson, K., Olson, L. and Ungerstedt, U., Ascending monoamine neurons to the telencephalon and diencephalon, Actaphysiol. scand., 67 (1966) 313–326.CrossRefGoogle Scholar
  5. 5.
    Beckstead, R. M., Convergent thalamic and mesencephalic projections to the anterior medial cortex in the rat, J. comp. Neurol., 166 (1976) 403–416.CrossRefGoogle Scholar
  6. 6.
    Beckstead, R. M., Afferent connections of the entorhinal area in the rat as demonstrated by retrograde cell-labeling with horseradish peroxidase, Brain Research, 152 (1978) 249–264.CrossRefGoogle Scholar
  7. 7.
    Berger, B., Thierry, A. M., Tassin, J. P. and Myre, M. A., Dopaminergic innervation of the rat prefrontal cortex: a fluorescence histochemical study, Brain Research, 106 (1976) 133–145.CrossRefGoogle Scholar
  8. 8.
    Berman, A. L., The Brain Stem of the Cat. A Cytoarchitectonic Atlas with Stereotaxic Coordinates, University of Wisconsin Press, Madison, 1968.Google Scholar
  9. 9.
    Brownstein, M., Saavedra, J. M. and Palkovits, M., Norepinephrine and dopamine in the limbic system of the rat, Brain Resecrch, 79 (1974) 431–436.CrossRefGoogle Scholar
  10. 10.
    Bunney, B. S. and Aghajanian, G. K., The precise localization of nigral afferents in the rat as determined by a retrograde tracing technique, Brain Research, 117 (1976) 423–436.CrossRefGoogle Scholar
  11. 11.
    Carpenter, M. B., Nakano, K. and Kim, R., Nigrothalamic projections in the monkey demonstrated by autoradiographic technics, J. comp. Neurol., 165 (1976) 401–416.CrossRefGoogle Scholar
  12. 12.
    Carpenter, M. B. and Peter, P., Nigrostriatal and nigrothalamic fibers in the rhesus monkey, J. comp. Neurol., 144 (1972) 93–116.CrossRefGoogle Scholar
  13. 13.
    Cole, M., Nauta, W. J. H. and Mehler, W. R., The ascending efferent projections of the substantia nigra, Trans. Amer, neurol. Ass., 89 (1964) 74–78.Google Scholar
  14. 14.
    Connor, J. D., Caudate unit responses to nigral stimuli: evidence for a possible nigro-neostriatal pathway, Science, 130 (1968) 899–900.CrossRefGoogle Scholar
  15. 15.
    Dahlström, A. and Fuxe, K., Evidence for the existence of monoamine-containing neurons in the central nervous system, Acta physiol scand., Suppl. 232 (1964) 1–55.Google Scholar
  16. 16.
    De Olmos, J. S. and Ingram, W. R., The projection field of the stria terminalis in the rat brain, J. comp. Neurol., 146 (1972) 303–334.CrossRefGoogle Scholar
  17. 17.
    Domesick, V. B., The topographic organization of the striatonigral connection in the rat (Abstr.), Anat. Rec., 187 (1977) 567.Google Scholar
  18. 18.
    Domesick, V. B., Beckstead, R. M. and Nauta, W. J. H., Some ascending and descending projections of the substantia nigra and ventral tegmental area in the rat, Neurosci. Abstr., II (1976) 61.Google Scholar
  19. 19.
    Fallon, J. H. and Moore, R. Y., Catecholamine innervation of the basal forebrain. IV. Topography of the dopamine projection to the basal forebrain and neostriatum, J. comp. Neurol., 180 (1978) 545–580.CrossRefGoogle Scholar
  20. 20.
    Faull, R. L. M. and Carman, J. B., Ascending projections of the substantia nigra in the rat, J. comp. Neurol., 132 (1968) 73–92.CrossRefGoogle Scholar
  21. 21.
    Faull, R. L. M. and Mehler, W. R., Studies of the fiber connections of the substantia nigra in the rat using the method of retrograde transport of horseradish peroxidase, Neurosci. Abstr., II (1976) 62.Google Scholar
  22. 22.
    Ferraro, A., The connections of the pars suboculomotorica of the substantia nigra, Arch. Neurol. Psychiat. (Chic), 19 (1928) 177–180.Google Scholar
  23. 23.
    Fibiger, H. C., Pudritz, R. E. McGeer, P. L. and McGeer, E. G., Axonal transport in nigro-striatal and nigro-thalamic neurons: effects of medial forebrain bundle lesions and 6-hydroxydopamine, J. Neurochem., 19 (1972) 1697–1708.CrossRefGoogle Scholar
  24. 24.
    Fox, C. A., The stria terminalis, longitudinal association bundle and precommissural fornix fibers in the cat, J. comp. Neurol., 79 (1943) 277–295.CrossRefGoogle Scholar
  25. 25.
    Fox, C. A., Rafols, J. A. and Cowan, W. M., Computer measurements of axis cylinder of radial fibers and ‘comb’ bundle fibers, J. comp. Neurol., 159 (1975) 201–224.CrossRefGoogle Scholar
  26. 26.
    Fox, C. A. and Schmitz, J. T., The substantia nigra and the entopeduncular nucleus in the cat, J. comp. Neurol., 80 (1944) 323–334.CrossRefGoogle Scholar
  27. 27.
    Frigyesi, T. L. and Purpura, D. F., Electrophysiological analysis of reciprocal caudatonigral relations, Brain Research, 6 (1967) 440–456.CrossRefGoogle Scholar
  28. 28.
    Fuxe, K., Evidence for the existence of monoamine nerve terminals in the central nervous system. IV. Distribution of dopamine nerve terminals in the central nervous system, Acta physiol. scand., 64, Suppl. 247 (1965) 39–85.Google Scholar
  29. 29.
    Fuxe, K., Hökfelt, T., Johansson, O., Jonsson, G., Lidbrink, P. and Ljungdahl, A., The origin of the dopamine nerve terminals in limbic and frontal cortex. Evidence for mesocortical dopamine neurons, Brain Research, 82 (1974) 349–355.CrossRefGoogle Scholar
  30. 30.
    Graybiel, A. M., Organization of the nigrotectal connection: an experimental tracer study in the cat, Brain Research, 143 (1978) 339–348.CrossRefGoogle Scholar
  31. 31.
    Graybiel, A. M. and Sciascia, T. R., Origin and distribution of nigrotectal fibers in the cat, Neurosci. Abstr., 1 (1975) 174.Google Scholar
  32. 32.
    Hedreen, J. C., Separate demonstration of dopaminergic anc non-dopaminergic projections of substantia nigra in the rat (Abstr.), Anat. Rec, 169, Vol. 2 (1971) 338.Google Scholar
  33. 33.
    Hedreen, J. C., and Chalmers, J. P., Neuronal degeneration in the rat brain induced by 6-hydroxydopamine: a histological and biochemical study, Brain Research, 47 (1972) 1–36.CrossRefGoogle Scholar
  34. 34.
    Heimer, L. and Wilson, R. D., The subcortical projections of the allocortex: similarities in the neural associations of the hippocampus, the piriform cortex, and the neocortex. In M. Santini (Ed.), Golgi Centennial Symposium, Raven Press, New York, 1975, pp. 177–193.Google Scholar
  35. 35.
    Herkenham, M., The nigro-thalamo-cortical connection mediated by the nucleus ventralis medialis thalami: evidence for a wide cortical distribution in the rat, Anat. Rec, 184 no. 3 (1976) 426.Google Scholar
  36. 36.
    Herkenham, M., The connections of the nucleus reuniens thalami: evidence for a direct thalamo-hippocampal pathway in the rat, J. comp. Neurol., 177 (1977) 589–610.CrossRefGoogle Scholar
  37. 37.
    Herkenham, M. and Nauta, W. J. H., Afferent connections of the habenular nuclei in the rat. A horseradish peroxidase study, with a note on the fiber-of-passage problem, J. comp. Neurol., 173 (1977) 123–146.CrossRefGoogle Scholar
  38. 38.
    Hökfelt, T. and Ungerstedt, U., Electron and fluorescence microscopical studies on the nucleus caudatus putamen of the rat after unilateral lesions of ascending nigro-neostriatal dopamine neurons, Acta physiol. scand., 16 (1969) 415–426.CrossRefGoogle Scholar
  39. 39.
    Holmes, J. M., The nervous system of a dog without a forebrain, J. Physiol. (Lond.), 27 (1901) 1–25.Google Scholar
  40. 40.
    Hopkins, D. A. and Niessen, L. W., Substantia nigra projections to the reticular formation, superior colliculus and central gray in the rat, cat and monkey, Neu osci. Lett., 2 (1976) 253–259.CrossRefGoogle Scholar
  41. 41.
    Hull, C. D., Barnardi, G. and Buchwald, N. A., Intracellular responses of caudate neurons to brain stem stimulation, Brain Research, 22 (1970) 163–179.CrossRefGoogle Scholar
  42. 42.
    Jayaraman, A., Batton, B. R. IIIrd and Carpenter, M. B., Nigrotectal projections in the monkey: an autoradiographic study, Brain Research, 135 (1977) 147–152.CrossRefGoogle Scholar
  43. 43.
    Kizer, J. S., Palkovits, M. and Brownstein, M. J., The projections of the A8, A9 and AlO dopaminergic cell bodies: evidence for a nigral-hypothalamic-median eminence pathway, Brain Research, 108 (1976) 363–370.CrossRefGoogle Scholar
  44. 44.
    Krettek, J. E. and Price, J. L., Projections from the amygdala to the perirhinal and entorhinal cortices and the subiculum, Brain Research, 71 (1974) 150–154.CrossRefGoogle Scholar
  45. 45.
    Lindvall, O. and Björklund, A., The organization of the ascending catecholamine neuron systems in the rat brain, Actaphysiol. scand., Suppl. 412 (1974) 1–48.Google Scholar
  46. 46.
    Lindvall, O., Björklund, A., Moore, R. Y. and Stenevi, U., Mesencephalic dopamine neurons projecting to neocortex, Brain Research, 81 (1974) 325–331.CrossRefGoogle Scholar
  47. 47.
    Lindvall, O., Björklund, A., Nobin, A. and Stenevi, U., The adrenergic innervation of the rat thalamus as revealed by the glyoxylic acid method, J. comp. Neurol., 154 (1974) 317–348.CrossRefGoogle Scholar
  48. 48.
    McLennon, H., The release of dopamine from the putamen, Experientia (Basel), 21 (1965) 725.CrossRefGoogle Scholar
  49. 49.
    Mettler, F. A., Extensive unilateral cerebral removals in the primate: physiologic effects and resultant degeneration, J. comp. Neurol., 79 (1943) 185–245.CrossRefGoogle Scholar
  50. 50.
    Mettler, F. A., Nigrofugal connections in the primate brain, J. comp. Neurol., 138 (1970) 291–320.CrossRefGoogle Scholar
  51. 51.
    Moore, R. Y., Bhatnagar, R. K. and Heller, A., Anatomical and chemical studies of a nigro-necstriatal projection in the cat, Brain Research, 30 (1971) 119–135.CrossRefGoogle Scholar
  52. 52.
    Nauta, H. J. W. and Cole, M., Efferent projections of the subthalamic nucleus: an autoradiographic study in monkey and cat, J. comp. Neurol., 180 (1978) 1–16.CrossRefGoogle Scholar
  53. 53.
    Nauta, W. J. H. and Domesick, V. B., Crossroads of limbic and striatal circuitry: hypothalamo-nigral connections. In K. E. Livingston and O. Hornykiewicz (Eds.), Limbic Mechanisms, Plenum Press, London, 1978.Google Scholar
  54. 54.
    Nauta, W. J. H. and Mehler, W. R., Projections of the lentiform nucleus in the monkey, Brain Research, 1 (1966) 3–42.CrossRefGoogle Scholar
  55. 55.
    Nauta, W. J. H., Smith, G. P., Faull, R. L. M. and Domesick, V. B., Efferent connections and nigral afférents of the nucleus accumbens septi in the rat, Neuroscience, 3 (1978) 385–401.CrossRefGoogle Scholar
  56. 56.
    Palkovits, M. and Jacobowitz, D. M., Topographic atlas of catecholamine and acetylcholin-esterase-containing neurons in the rat brain. II. Hindbrain (mesencephalon, rhombencephalon), J. comp. Neurol., 157 (1974) 29–52.CrossRefGoogle Scholar
  57. 57.
    Pasquier, D. A., Kemper, T. L., Forbes, W. B. and Morgane, P. J., Dorsal raphe, substantia nigra and locus coeruleus: interconnections with each other and the neostriatum, Brain Res. Bull, 2 (1977) 323–339.CrossRefGoogle Scholar
  58. 58.
    Portig, P. J. and Vogt, M., Activation of a dopaminergic nigro-striatal pathway, J. Physiol. (Lond.), 197(1968)20–21.Google Scholar
  59. 59.
    Raisman, J., Cowan, W. M. and Powell, T. P. S., An experimental analysis of the efferent projection of the hippocampus, Brain, 89 (1966) 83–108.CrossRefGoogle Scholar
  60. 60.
    Rinvik, E., Demonstration of nigro-thalamic connections in the cat by retrograde transport of horseradish peroxidase, Brain Research, 90 (1975) 313–318.CrossRefGoogle Scholar
  61. 61.
    Rinvik, E., Grovofá, I. and Otterson, O. P., Demonstration of nigrotectal and nigroreticular projections in the cat by axonal transport of proteins, Brain Research, 112 (1976) 388–394.CrossRefGoogle Scholar
  62. 62.
    Rosegay, H., An experimental investigation of the connections between the corpus striatum and substantia nigra in the cat, J. comp. Neurol., 80 (1944) 293–321.CrossRefGoogle Scholar
  63. 63.
    Simon, H. and Le Moal, M., Demonstration by the Fink-Heimer impregnation method of a ventral mesencephalic-locus coeruleus projection in the rat, Experientia, (Basel), 33 (1977) 614–615.CrossRefGoogle Scholar
  64. 64.
    Simon, H., Le Moal, M., Galey, D. and Cardo, B., Silver impregnation of dopaminergic systems after radiofrequency and 6-OHDA lesions of the rat ventral tegmentum, Brain Research, 115 (1976)215–231.CrossRefGoogle Scholar
  65. 65.
    Sprague, J. M. and Meyer, M., An experimental study of the fornix in the rabbit J. Anat. (Lond.), 84 (1950) 354–368.Google Scholar
  66. 66.
    Tassin, J. P., Cheramy, A., Blanc, G., Thierry, A. M. and Glowinski, J., Topographical distribution of dopaminergic innervation and of dopaminergic receptors in the rat striatum. I. Microestimation of [3H]dopamine uptake and dopamine content in microdiscs, Brain Research, 107 (1976) 291–301.CrossRefGoogle Scholar
  67. 67.
    Thierry, A. M., Blanc, G., Sobel, A., Stinus, L. and Glowinski, J., Dopaminergic terminals in the rat cortex, Science, 180 (1973) 499–501.CrossRefGoogle Scholar
  68. 68.
    Ungerstedt, U., Stereotaxic mapping of the monoamine pathways in the rat brain, Acta physiol scand, 197, Suppl. 367 (1971) 1–48.Google Scholar
  69. 69.
    Versteeg, D. H. G., van der Gugten, J., de Jong, W. and Palkovits, M., Regional concentrations of noradrenaline and dopamine in rat brain, Brain Research, 113 (1976) 563–574.CrossRefGoogle Scholar
  70. 70.
    York, D. H., Possible dopaminergic pathway from substantia nigra to putamen, Brain Research, 20 (1969) 233–249.CrossRefGoogle Scholar

Copyright information

© Elsevier/North-Holland Biomedical Press 1993

Authors and Affiliations

  • Robert M. Beckstead
    • 1
    • 2
  • Valerie B. Domesick
    • 1
    • 2
  • Walle J. H. Nauta
    • 1
    • 2
  1. 1.Department of PsychologyMassachusetts Institute of TechnologyCambridgeUSA
  2. 2.(V.B.D.) Mailman Research CenterMcLean HospitalBelmontUSA

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