Dopaminergic innervation of the pallidum in the normal state, in MPTP-treated monkeys and in parkinsonian patients

Authors

  • Caroline Jan,

    1. INSERM U289, Mécanismes et Conséquences de la Mort Neuronale, Hôpital de la Salpêtrière, 47 Boulevard de l'Hôpital, 75013, Paris, France
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  • Chantal François,

    1. INSERM U289, Mécanismes et Conséquences de la Mort Neuronale, Hôpital de la Salpêtrière, 47 Boulevard de l'Hôpital, 75013, Paris, France
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  • Dominique Tandé,

    1. INSERM U289, Mécanismes et Conséquences de la Mort Neuronale, Hôpital de la Salpêtrière, 47 Boulevard de l'Hôpital, 75013, Paris, France
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  • Jérôme Yelnik,

    1. INSERM U289, Mécanismes et Conséquences de la Mort Neuronale, Hôpital de la Salpêtrière, 47 Boulevard de l'Hôpital, 75013, Paris, France
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  • Léon Tremblay,

    1. INSERM U289, Mécanismes et Conséquences de la Mort Neuronale, Hôpital de la Salpêtrière, 47 Boulevard de l'Hôpital, 75013, Paris, France
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  • Yves Agid,

    1. INSERM U289, Mécanismes et Conséquences de la Mort Neuronale, Hôpital de la Salpêtrière, 47 Boulevard de l'Hôpital, 75013, Paris, France
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  • Etienne Hirsch

    1. INSERM U289, Mécanismes et Conséquences de la Mort Neuronale, Hôpital de la Salpêtrière, 47 Boulevard de l'Hôpital, 75013, Paris, France
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*: Dr C. François, as above.
E-mail: cfrancoi@ccr.jussieu.fr

Abstract

The aim of the present study was to characterize the dopaminergic innervation of the pallidum in primates (humans and Cercopithecus aethiops). Firstly, in monkeys, biotin dextran amine was injected into dopaminergic areas, and the anterogradely labelled axons were reconstructed from serial sections and analysed in the pallidum. Secondly, in parkinsonian patients and MPTP-treated monkeys, the dopaminergic innervation of the pallidum was studied using tyrosine hydroxylase-positive fibre quantification. Our study revealed that dopaminergic areas A8 and A9 innervated the two pallidal segments. Individual axonal arborizations displayed a great heterogeneity. Some dopaminergic axons crossed the pallidum without branching, other axons made small terminal arborizations in a restricted region of one pallidal segment, whereas others developed dense arborizations covering extended areas in the two pallidal segments. This heterogeneous organization suggests that dopamine could directly modulate the pallidum using either a point-to-point or a diffuse projection pattern. A statistically significant loss of dopaminergic fibres in the internal (−43%) and external pallidum (−39.6%) of humans, and in the internal (−54.3%) and external pallidum (−59%) of monkeys was revealed in parkinsonian states. The consequences of this alteration are still unknown but it might participate in the triggering of motor symptoms observed in Parkinson's disease.

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