The human substantia nigra and ventral tegmental area. A neuroanatomical study with notes on aging and aging diseases

The present study comprises a cytoarchitectonic analysis of the human substantia nigra (SN) and ventral tegmental area (VTA); a discussion of their chemoarchitecture and fiber connections (mainly based on tract-tracing studies in primates) preceded by an overview of the wealth of tract-tracing data in rodents; a discussion of the involvement of the SN/VTA complex in Parkinson's disease (PD) and related disorders and in Alzheimer's disease (AD), including some quantitative data; and finally, some functional and pathophysiological considerations, relating nigral organization to pathophysiology and hypotheses on the etiology and distribution of AD and PD. DAergic cell populations in the mesencephalon (SN pars compacta, VTA, and the retrorubral area A8) which give rise to well-developed, DAergic, mesotelencephalic pathways, including a distinct mesostriatal system, and a substance P-immunoreactive striatotegmental system which projects to the SN pars reticulata and VTA appear to be common to reptiles, birds, and mammals (Sect. 3.1). The extensive literature on the organization of the SN/VTA complex in rats is summarized in Sect. 3.2. The mesotelencephalic projection is organized along inverted dorsal to ventral, medial to lateral, and rostral to caudal topographies. A dense DAergic innervation is characteristic of the entire striatal complex, including the caudate-putamen (the dorsal striatum), the nucleus accumbens, and the olfactory tubercle (the ventral striatum). This mesostriatal projection is compartmentally organized with distinct sets of DAergic neurons projecting to striosomes and extrasriosomal matrix, respectively, suggesting specialized channels directed at DAergic modulation of sensorimotor processing in the striatal matrix and limbic related mechanisms represented in the striosomal system. The VTA and medial part of the SN give rise to the DAergic mesolimbocortical system with extensive projections to limbic, allocortical, and neocortical structures. The striatonigral output pattern in rats is organized in such a way that the dorsal striatum mainly innervates the SN pars reticulata, whereas the ventral striatum projects predominantly to the VTA and medial part of the SN. Within the striatonigral projections in rats some interesting channels can be recognized, relating the sensorimotor cortex, via its corticostriatal projections, to that region of the SN giving rise to the nigrothalamic projection, and the visual cortex to the nigrotectal component of the SN pars reticulata.(ABSTRACT TRUNCATED AT 400 WORDS)