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Distinctive Chemoanatomical and Developmental Features of the Prefrontal Dopaminergic System in Primates as Compared to Rodents

  • B. Berger
Conference paper
Part of the Research and Perspectives in Neurosciences book series (NEUROSCIENCE)

Abstract

Phylogenetic considerations of the dopaminergic (DA) innervation of the prefrontal cortex illustrate the pitfalls of extrapolating data obtained in rodent brain to human or nonhuman primates, as has been the case for about 15 years. Comparative studies of prefrontal DA innervation in rats and primates are complicated by several features; including the lack in rodents of a frontal area strictly homologous to the primate prefrontal cortex, the heterogeneity of the dopaminergic population which provides the cortical projections in rats, and the major evolutionary changes of the cortical DA innervation in primates. The main distinctive features between rats and primates with respect to prefrontal DA innervation are reviewed in this paper, and the value of the rat as a representative model for that study is further discussed.

Keywords

Prefrontal Cortex Tyrosine Hydroxylase Anterior Cingulate Cortex Ventral Tegmental Area Ventral Mesencephalon 
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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References

  1. Amaral DG, Price JL (1984) Amygdalo-cortical projections in the monkey (Macaca fascicularis). J Comp Neurol 230:465–496PubMedCrossRefGoogle Scholar
  2. Baleydier C, Mauguière F (1980) The duality of the cingulate gyrus in monkey: neuroanatomical study and functional hypothesis. Brain 103:525–554PubMedCrossRefGoogle Scholar
  3. Barbas H, Haswell Henion TH, Dermon CR (1991) Diverse thalamic projections to the prefrontal cortex in the rhesus monkey. J Comp Neurol 313:65–94PubMedCrossRefGoogle Scholar
  4. Bean AJ, Roth RH (1991) Extracellular dopamine and neurotensin in rat prefrontal cortex in vivo. Effects of median forebrain bundle stimulation frequency, stimulation pattern and dopamine autoreceptors. J Neurosci 11:2694–2702PubMedGoogle Scholar
  5. Bean AJ, Dagerlind A, Hökfelt T, Dobner PR (1992) Cloning of human neurotensin/neuromedin N genomic sequences and expression in the ventral mesencephalon of schizophrenics and age/sex matched controls. Neuroscience 50:259–269PubMedCrossRefGoogle Scholar
  6. Berger B, Thierry AM, Tassin JP, Moyne MA (1976) Dopaminergic innervation of the rat prefrontal cortex: a fluorescence histochemical study. Brain Res 106:133–145PubMedCrossRefGoogle Scholar
  7. Berger B, Vemey C, Alvarez C, Vigny A, Helle KB (1985a) New dopaminergic terminal fields in the motor, visual (area 18b) and retrosplenial cortex in the young and adult rat. Immuno- cytochemical and catecholamine histochemical analyses. Neuroscience 15:983–998PubMedCrossRefGoogle Scholar
  8. Berger B, Verney C, Febvret A, Vigny A, Helle KB (1985b) Postnatal ontogenesis of the dopaminergic innervation in the rat anterior cingulate cortex (area 24). Immunocytochemical and catecholamine fluorescence histochemical analysis. Dev Brain Res 21:31–47CrossRefGoogle Scholar
  9. Berger B, Verney C, Gaspar P, Febvret A (1985c) Transient expression of tyrosine hydroxylase immunoreactivity in some neurons of the rat neocortex during postnatal development. Dev Brain Res 23:141–144CrossRefGoogle Scholar
  10. Berger B, Trottier S, Gaspar P, Verney C, Alvarez C (1986) Major dopamine innervation of the cortical motor areas in the cynomolgus monkey. A radioautographic study with comparative assessment of serotoninergic afferents. Neurosci Let 72:121–127CrossRefGoogle Scholar
  11. Berger B, Trottier S, Verney C, Gaspar P, Alvarez C (1988) Regional and laminar distribution of the dopamine and serotonin innervation in macaque cerebral cortex. A radioautographic study. J Comp Neurol 273:99–119PubMedCrossRefGoogle Scholar
  12. Berger B, Febvret A, Greengard P, Goldman-Rakic PS (1990) DARPP-32, a phosphoprotein enriched in dopaminoceptive neurons bearing dopamine D1 receptors: distribution in the cerebral cortex of the newborn and adult rhesus monkey. J Comp Neurol 299:327–348PubMedCrossRefGoogle Scholar
  13. Berger B, Gaspar P, Verney C (1991) Dopaminergic innervation of the cerebral cortex: unexpected differences between rodents and primates. TINS 14:21–27PubMedGoogle Scholar
  14. Berger B, Verney C, Goldman-Rakic PS (1992) Prenatal monoaminergic innervation of the cerebral cortex; differences between rodents and primates. In: Kostovic I, Knezevic S, Spilich G (eds) Neurodevelopment, aging and cognition. Birkhauser, Boston, pp 18–36Google Scholar
  15. Bouthenet ML, Souil E, Martres MP, Sokoloff P, Giros B, Schwartz JC (1991) Localization of dopamine D3 receptor mRNA in the rat brain using in situ hybridization histochemistry: comparison with dopamine D2 receptor mRNA. Brain Res 564:203–219PubMedCrossRefGoogle Scholar
  16. Brozoski TJ, Brown RM, Rosvold HE, Goldman PS (1979) Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey. Science 205:929–932PubMedCrossRefGoogle Scholar
  17. Cepeda C, Radisavljevic Z, Peacock W, Levine MS, Buchwald NA (1992) Differential modulation by dopamine of responses evoked by excitatory aminoacids in human cortex. Synapse 11:330–341PubMedCrossRefGoogle Scholar
  18. Civelli O, Bunzow JR, Grandy DK, Zhou QY, Van Tol HHM (1991) Molecular biology of the dopamine receptors. Eur J Pharmacol 207:277–286PubMedCrossRefGoogle Scholar
  19. Clark FM, Proudfit HK (1992) Anatomical evidence for genetic differences in the innervation of the rat spinal cord by noradrenergic locus coeruleus neurons. Brain Res 591:44–53PubMedCrossRefGoogle Scholar
  20. De Keyser J, Ebinger G, Vauquelin G (1989) Evidence for a widespread dopaminergic innervation of the human cerebral cortex. Neurosci Lett 104:281–285PubMedCrossRefGoogle Scholar
  21. Descarries L, Lemay B, Doucet G, Berger B (1987) Regional and laminar density of the dopamine innervation in adult rat cerebral cortex. Neuroscience 21:807–824PubMedCrossRefGoogle Scholar
  22. Deutch AY, Goldstein M, Baldino F, Roth RH (1988) Telencephalic projections of the A8 dopamine cell group. In: Mesocorticolimbic dopamine system. Ann NY Acad Sci 537:27–50PubMedCrossRefGoogle Scholar
  23. Deutch AY, Clark WA, Roth RH (1990) Prefrontal cortical dopamine depletion enhances the responsiveness of mesolimbic dopamine neurons to stress. Brain Res 521:311–315PubMedCrossRefGoogle Scholar
  24. Dubach M, Schmidt R, Kunkel D, Bowden DM, Marti R, German DC (1987) Primate neostriatal neurons containing tyrosine hydroxylase: immunohistochemical evidence. Neurosci Lett 75:205–210PubMedCrossRefGoogle Scholar
  25. Fallon JH, Loughlin SE (1987) Monoamine innervation of cerebral cortex and a theory of the role of monoamines in cerebral cortex and basal ganglia. In: Jones EG, Peters A (eds) Cerebral cortex. Vol 6. Plenum Press, New York, pp 41–127Google Scholar
  26. Febvret A, Berger B, Gaspar P, Verney C (1991) Further indication that distinct dopaminergic subsets project to the rat cerebral cortex: lack of colocalization with neurotensin in the superficial dopaminergic fields of the anterior cingulate, motor, retrosplenial and visual cortices. Brain Res 547:37–52PubMedCrossRefGoogle Scholar
  27. Gaspar P, Berger B, Febvret A, Vigny A, Krieger-Poulet M, Borri-Voltattorni C (1987) Tyrosine hydroxylase immunoreactive neurons in the human cerebral cortex: a novel cate- cholaminergic group? Neurosci Lett 80:257–262PubMedCrossRefGoogle Scholar
  28. Gaspar P, Berger B, Febvret A, Vigny A, Henry JP (1989) Catecholamine innervation of the human cerebral cortex as revealed by comparative immunohistochemistry of tyrosine hydroxylase and dopamine-β-hydroxylase. J Comp Neurol 279:249–271PubMedCrossRefGoogle Scholar
  29. Gaspar P, Berger B, Febvret A (1990) Neurotensin innervation of the human cerebral cortex: lack of colocalization with catecholamines. Brain Res 530:181–195PubMedCrossRefGoogle Scholar
  30. Gaspar P, Duyckaerts C, Alvarez C, Javoy-Agid F, Berger B (1991) Alterations of dopaminergic and noradrenergic innervations in motor cortex in Parkinson’s disease. Ann Neurol 30:365–374PubMedCrossRefGoogle Scholar
  31. Gaspar P, Stepniewska I, Kaas J (1992) Topography and collateralization of the dopaminergic projections to motor and lateral prefrontal cortex in Owl monkeys. J Comp Neurol 325:1–21PubMedCrossRefGoogle Scholar
  32. German DC, Manaye K, Smith WK, Woodward DJ, Saper CB (1989) Midbrain dopaminergic cell loss in Parkinson’s disease: computer visualization. Ann Neurol 26:597–514CrossRefGoogle Scholar
  33. Godbout R, Mantz J, Pirot S, Glowinski J, Thierry AM (1991) Inhibitory influence of the mesocortical dopaminergic neurons on their target cells: electrophysiological and pharmacological characterization. J Pharmacol Exp Therap 258:728–738Google Scholar
  34. Goldman-Rakic PS (1987) Circuitry of primate prefrontal cortex and regulation of behavior by representational memory. In: Plum F, Mountcastle V (eds) Handbook of physiology. Bethesda, MD, American Physiol Soc, Vol 5, 373–417Google Scholar
  35. Goldman-Rakic PS, Porrino LJ (1985) The primate mediodorsal (MD) nucleus and its projections to the frontal lobe. J Comp Neurol 242:535–560PubMedCrossRefGoogle Scholar
  36. Goldman-Rakic PS, Leranth C, Williams SM, Mons N, Geffard M (1989) Dopamine synaptic complex with pyramidal neurons in primate cerebral cortex. Proc Natl Acad Sci 86:9015–9019PubMedCrossRefGoogle Scholar
  37. Goldman-Rakic PS, Lidow MS, Gallager DW (1990) Overlap of dopaminergic, adrenergic and serotoninergic receptors and complementarity of their subtypes in primate prefrontal cortex. J Neurosci 10:2125–2139PubMedGoogle Scholar
  38. Grandy DK, Zhang Y, Bouvier C, Zhou QY, Johnson RA, Allen L, Buck K, Bunzow JR, Salon J, Civelli O (1991) Multiple human D5 dopamine receptor genes: a functional receptor and two pseudogenes. Proc Nat Acad Sci 88:9175–9179PubMedCrossRefGoogle Scholar
  39. Halliday GM, Törk I (1986) Comparative anatomy of the ventromedial mesencephalic tegmentum in the rat, cat, monkey and human. J Comp Neurol 52(4):423–445CrossRefGoogle Scholar
  40. Hara Y, Shiosaka S, Senba E, Sakanaka A, Inagaki S, Takagi H, Kawai Y, Takatsuki K, Matsuzaki T, Tohyama M (1982) Ontogeny of the neurotensin-containing neuron system of the rat: immunohistochemical analysis. 1 forebrain and diencephalon. J Comp Neurol 208:177–195PubMedCrossRefGoogle Scholar
  41. Hemmings HC, Walaas SI, Ouimet CC, Greengard P (1987) Dopaminergic regulation of protein phosphorylation in the striatum: DARPP 32. TINS 10:377–383Google Scholar
  42. Hoffman MA (1985) Size and shape of the cerebral cortex in mammals. 1. The cortical surface. Brain Behav Evol 27:28–40CrossRefGoogle Scholar
  43. Hornung JP, Törk I, Detribolet N (1989) Morphology of tyrosine hydroxylase immunoreactive neurons in the human cerebral cortex. Exp Brain Res 76:12–20PubMedCrossRefGoogle Scholar
  44. Huntley GW, Morrison JH, Prikhozhan A, Sealfon SC (1992) Localization of multiple dopamine receptor subtype messenger RNAs in human and monkey motor cortex and striatum. Mol Brain Res 15:181–188PubMedCrossRefGoogle Scholar
  45. Iacovitti L, Lee J, Joh TH, Reis DJ (1987) Expression of tyrosine hydroxylase in neurons of cultured cerebral cortex: evidence for phenotypic plasticity in neurons of the CNS. J Neurosci 74:1264–1270Google Scholar
  46. Kalsbeek A, Voorn P, Buijs RM, Pool CW, Uylings MBM (1988) Development of the dopaminergic innervation in the prefrontal cortex of the rat. J Comp Neurol 269:58–72PubMedCrossRefGoogle Scholar
  47. Köhler C, Everitt BJ, Pearson J, Goldstein M (1983) Immunohistochemical evidence for a new group of catecholamine containing neurons in the basal forebrain of the monkey. Neurosci Lett 37:161–166PubMedCrossRefGoogle Scholar
  48. Krettek JE, Price JL (1977) The cortical projections of the mediodorsal nucleus and adjacent thalamic nuclei in the rat. J Comp Neurol 17:157–192CrossRefGoogle Scholar
  49. Kuljis RO, Martin-Vasallo P, Peress NS (1989) Lewy bodies in tyrosine hydroxylase-synthesizing neurons of the human cerebral cortex. Neurosci Lett 106:49–54PubMedCrossRefGoogle Scholar
  50. Leonard CM (1969) The prefrontal cortex of the rat. 1. Cortical projection of the mediodorsal nucleus. 2. Efferent connections. Brain Res 12:321–343PubMedCrossRefGoogle Scholar
  51. Lewis DA, Campbell MJ, Foote SL, Goldstein M, Morrison JH (1987) The distribution of tyrosine hydroxylase immunoreactive fibers in primate neocortex is widespread but regionally specific. J Neurosci 7:279–290PubMedGoogle Scholar
  52. Lewis DA, Foote SL, Golstein M, Morrison JH (1988a) The dopaminergic innervation of monkey prefrontal cortex: a tyrosine hydroxylase immunohistochemical study. Brain Res 449:225–243PubMedCrossRefGoogle Scholar
  53. Lewis DA, Morrison JH, Goldstein M (1988b) Brainstem dopaminergic neurons project to monkey parietal cortex. Neurosci Lett 86:11–16PubMedCrossRefGoogle Scholar
  54. Lewis DA, Melchitzky DS, Gioio A, Solomon Z, Kaplan BB (1991) Neuronal localization of tyrosine hydroxylase gene products in human neocortex. Mol Cell Neurosci 2:228–234PubMedCrossRefGoogle Scholar
  55. Lindvall O, Björklund A, Divac I (1978) Organization of catecholamine neurons projecting to the frontal cortex in the rat. Brain Res 142:1–24PubMedCrossRefGoogle Scholar
  56. Louilot A, Taghzouti K, Simon H, Le Moal M (1989) Limbic system, basal ganglia and dopaminergic neurons. Executive and regulatory neurons and their role in the organization of behavior. Brain Behav Evol 33:157–161PubMedCrossRefGoogle Scholar
  57. Marin-Padilla M (1984) Neurons of Layer I. A developmental analysis. In: Peters A and Jones EG ed. Cerebral cortex, Vol 1, Plenum Press, New York, pp 447–478Google Scholar
  58. Meador-Woodruff JH, Mansour A, Grandy DK, Damask SP, Civelli O, Watson Jr SJ (1992) Distribution of D5 dopamine receptor mRNA in rat brain. Neurosci Lett 145:209–212PubMedCrossRefGoogle Scholar
  59. Mufson EJ, Mesulam MM (1984) Thalamic connections of the insula in the rhesus monkey and comments on the paralimbic connectivity of the medial pulvinar nucleus. J Comp Neurol 227:109–120PubMedCrossRefGoogle Scholar
  60. Oeth KM, Lewis DA (1992) Cholecystokinin- and dopamine-containing mesencephalic neurons provide distinct projections to monkey prefrontal cortex. Neurosci Lett 145:87–92PubMedCrossRefGoogle Scholar
  61. Ouimet CC, Miller PE, Hemmings HC, Walaas SJ, Greengard P (1984) DARPP-32, a dopamine and adenosine 3′5′monophosphate regulated phosphoprotein enriched in dopamine- innervated brain regions. III. Immunocytochemical localization. J Neurosci 4:111–124PubMedGoogle Scholar
  62. Palacios JM, Savasta M, Mengod G (1989) Does cholecystokinin colocalize with dopamine in the human substantia nigra? Brain Res 488:369–375PubMedCrossRefGoogle Scholar
  63. Park JK, Job TH, Ebner FF (1986) Tyrosine hydroxylase is expressed by neocortical neurons after transplantation. Proc Natl Acad Sci 83:7495–7498PubMedCrossRefGoogle Scholar
  64. Porrino LJ, Goldman-Rakic PS (1982) Brainstem innervation of prefrontal and anterior cingulate cortex in the rhesus monkey revealed by retrograde transport of HRP. J Comp Neurol 205:63–76PubMedCrossRefGoogle Scholar
  65. Retaux S, Besson MJ, Penit-Soria J (1991) Synergism between D1 and D2 dopamine receptors in the inhibition of the evoked release of H3 gaba in the rat prefrontal cortex. Neuroscience 43:323–330PubMedCrossRefGoogle Scholar
  66. Richfield EK, Young AB, Penney JB (1989) Comparative distributions of dopamine D1 and D2 receptors in the cerebral cortex of rats, cats and mokeys. J Comp Neurol 286:409–426PubMedCrossRefGoogle Scholar
  67. Satoh J, Suzuki K (1990) Tyrosine hydroxylase-immunoreactive neurons in the mouse cerebral cortex during the postnatal period. Dev Brain Res 53:1–5CrossRefGoogle Scholar
  68. Satoh H, Matsumura H (1990) Distribution of neurotensin-containing fibers in the frontal cortex of the macaque monkey. J Comp Neurol 298:215–223PubMedCrossRefGoogle Scholar
  69. Sawaguchi T, Goldman-Rakic PS (1991) D1 dopamine receptors in prefrontal cortex: involvement in working memory. Science 251:947–950PubMedCrossRefGoogle Scholar
  70. Schalling M, Friberg K, Seroogy K, Riederer P, Bird E, Schiffman SN, Mailleux P, Vand- erhaeghen JJ, Kuga S, Goldstein M, Kitahama K, Luppi PH, Jouvet M, Hökfelt T (1990) Analysis of expression of cholecystokinin in dopamine cells in the ventral mesencephalon of several species and in humans with schizophrenia. Proc Natl Acad Sci 87:8427–8431PubMedCrossRefGoogle Scholar
  71. Schell GR, Strick PL (1984) The origin of thalamic inputs to the arcuate premotor and supplementary motor areas. J Neurosci 4:539–560PubMedGoogle Scholar
  72. Seguela P, Watkins KC, Descarries L (1988) Ultrastructural features of dopamine axon terminals in the anteromedial and the suprarhinal cortex of adult rat. Brain Res 442:11–22PubMedCrossRefGoogle Scholar
  73. Seroogy KB, Dangaran K, Lim S, Haycock JW, Fallon JH (1989) Ventral mesencephalon neurons containing both cholecystokinin and tyrosine hydroxylase-like immunoreactivities project to forebrain regions. J Comp Neurol 279:397–414PubMedCrossRefGoogle Scholar
  74. Selemon LD, Goldman-Rakic PS (1988) Common cortical and subcortical targets of the dorsolateral prefrontal and posterior parietal cortices in the rhesus monkey: evidence for a distributed neural network subserving spatially guided behavior. J Neurosci 8:4049–4068PubMedGoogle Scholar
  75. Simon H, Scatton B, Le Moal M (1980) Dopaminergic A10 neurons are involved in cognitive functions. Nature 286:150–151PubMedCrossRefGoogle Scholar
  76. Smiley JF, Williams SM, Szigeti K, Goldman-Rakic PS (1992) Light and electron microscopic charecterization of dopamine immunoreactive axons in human cerebral cortex. J Comp Neurol 321:325–336PubMedCrossRefGoogle Scholar
  77. Stratford TR, Wirtshafter D (1990) Ascending dopaminergic projections from the dorsal raphe nucleus in the rat. Brain Res 511:173–176PubMedCrossRefGoogle Scholar
  78. Studier JM, Kitabgi P, Tramu G, Herve D, Glowinski J, Tassin JP (1988) Extensive colocalisation of neurotensin with dopamine in rat meso-cortico-frontal dopaminergic neurons. Neuropeptides 11:95–100CrossRefGoogle Scholar
  79. Taghzouti K, Simon H, Herve D, Blanc G, Studier JM, Glowinski J, Le Moal M, Tassin JP (1988) Behavioural deficits induced by an electrolytic lesion of the rat ventral mesencephalic tegmentum are corrected by a superimposed lesion of the dorsal noradrenergic system. Brain Res 440:172–176PubMedCrossRefGoogle Scholar
  80. Thal LJ, Laing K, Horowitz SG, Makman MH (1986) Dopamine stimulates rat cortical somatostatin release. Brain Res 372:205–209PubMedCrossRefGoogle Scholar
  81. Thierry AM, Blanc G, Sobel A, Stinus L, Glowinski J (1973) Dopaminergic terminals in the rat cortex. Science 182:499–501PubMedCrossRefGoogle Scholar
  82. Trottier S, Geffard M, Evrard B (1989) Co-localization of tyrosine hydroxylase and gaba immunoreactivities in human cortical neurons. Neurosci Lett 106:76–82PubMedCrossRefGoogle Scholar
  83. Van Eden CG, Hoorneman EMD, Buijs RM, Matthissen MAH, Geffard M, Uylings HBM (1987) Immunocytochemical localization of dopamine in the prefrontal cortex of the rat at the light and electronmicroscopic level. Neuroscience 22:849–862PubMedCrossRefGoogle Scholar
  84. Van Eden CG, Lamme VAF, Uylings HBM (1992) Heterotopic cortical afferents to the medial prefrontal cortex in the rat. A combined retrograde and anterograde tracer study. Eur J Neurosci 4:77–97PubMedCrossRefGoogle Scholar
  85. Van Tol HHM, Bunzow JR, Guan HC, Sunahara RK, Seeman P, Niznik HB, Civelli O (1991) Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature 350:610–614PubMedCrossRefGoogle Scholar
  86. Verney C, Berger B, Adrien J, Vigny A, Gay M (1982) Development of the dopaminergic innervation of the rat cerebral cortex. A light microscopic immunocytochemical study using antityrosine hydroxylase antibodies. Dev Brain Res 5:41–52CrossRefGoogle Scholar
  87. Verney C, Alvarez C, Geffard M, Berger B (1990) Ultrastructural double labeling study of dopamine terminals and gaba-containing neurons in rat anteromedial cerebral cortex. Eur J Neurosci 2:960–972PubMedCrossRefGoogle Scholar
  88. Vincent SR, Hope BT (1990) Tyrosine hydroxylase containing neurons lacking aromatic amin- oacid decarboxylase in the hamster brain. J Comp Neurol 295:290–298PubMedCrossRefGoogle Scholar
  89. Yang CR, Mogenson GJ (1990) Dopaminergic modulation of cholinergic responses in rat medial prefrontal cortex. An electrophysiological study. Brain Res 524:271–281PubMedCrossRefGoogle Scholar
  90. Yoshida M, Shirouzu M, Tanaka M, Semba K, Fibiger HC (1989) Dopaminergic neurons in the nucleus raphe dorsalis innervate the prefrontal cortex in the rat: a combined retrograde tracing and immunohistochemical study using antidopamine serum. Brain Res 496:373–376PubMedCrossRefGoogle Scholar
  91. Zecevic N, Verney C, Milosevic A, Berger B (1991) First description of the central catecholamine systems in 6–8 week-old human embryos. Soc Neurosci Abst 17:745Google Scholar
  92. Zhu ZQ, Armstrong DL, Grossman RG, Hamilton WJ (1990) Tyrosine hydroxylase- immunoreactive neurons in the temporal lobe in complex partial seizures. Ann Neurol 27:564–572PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • B. Berger
    • 1
  1. 1.INSERM U106, Bâtiment de PédiatrieHôpital SalpêtrièreParis Cedex 13France

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