This study on the human midbrain examines how specific neuroanatomical structures are involved in the aging process and in certain degenerative diseases of the nervous system.

1 Introduction.- 2 Materials and Techniques.- 2.1 Cytoarchitectonic Analysis.- 2.2 Quantitative Analysis.- 2.3 Immunohistochemical Procedures.- 2.4 Neuropathological Procedures.- 3 Comparative and Developmental Notes.- 3.1 The SN and VTA in Lower Tetrapods.- 3.2 The Mammalian SN and VTA.- 3.2.1 Cytoarchitecture.- 3.2.2 Cytology.- 3.2.3 Chemoarchitecture.- 3.2.4 Fiber Connections.- 3.2.4.1 Striomesencephalic Projections.- 3.2.4.2 Non-Striatal Afferents to the SN and VTA.- 3.2.4.3 Mesotelencephalic Projections.- 3.2.4.4 Nigrothalamic, Nigrotectal and Nigrotegmental Projections.- 3.2.5 A Summary of Nigral Organization.- 3.3 Development of the SN and VTA.- 4 The Human Substantia Nigra and Ventral Tegmental Area.- 4.1 Introduction.- 4.2 Cytological Features.- 4.3 Cytoarchitectonic Subdivision.- 4.3.1 Neuromelanin as a Marker for DAergic Neurons.- 4.3.2 Pigmentoarchitecture.- 4.3.3 Cytoarchitecture.- 4.4 Chemoarchitecture.- 4.5 Fiber Connections of the Primate SN Complex.- 4.5.1 Striatonigral Projections.- 4.5.2 Mesotelencephalic Projections.- 4.5.3 Nigrothalamic, Nigrotectal, and Nigrotegmental Projections.- 4.6 A Model of Human Nigral Organization.- 5 Neuropathological Aspects.- 5.1 Introduction.- 5.2 Involvement of the SN and VTA in Basal Ganglia Diseases.- 5.3 Involvement of the SN and VTA in AD.- 6 Quantitative Aspects.- 6.1 Introduction.- 6.2 Age-Related Neuronal Loss.- 6.3 Neuronal Loss in the SN and VTA in AD and PD.- 7 Functional and Pathophysiological Considerations.- 7.1 Lesion Studies on the SN.- 7.2 Some Functional and Pathophysiological Aspects of Mesencephalic DAergic Projections.- 7.2.1 Mesolimbocortical Circuitry and Cognition.- 7.2.2 Motor and Complex Cortico-Subcortical Loops.- 7.2.3 Imaging Studies.- 7.3 The Involvement of the SN and VTA in AD and PD.- 8 Summary.- Acknowledgements.- References.