The development of animal models of Parkinson’s disease (PD) is important to test new neuroprotective agents and strategies. Neurological disorders in humans can be modeled in animals using standardized procedures that recreate specific pathogenic events and their behavioral outcomes. The nigral neurons most severely affected in Parkinson's disease are the ventral tier cells that project to the matrix and form deep clusters in the substantia nigra pars reticulata. In humans, the compartmental specificity of the nigrostriatal pathway is revealed by the fact that the matrix compartment is densely innervated by dopaminergic fibers, whereas the striosomes display different densities of dopaminergic terminals depending on their location within the striatum. Furthermore, some nigrostriatal axons send collaterals both to thalamus and to brainstem pedunculopontine tegmental nucleus. The dorsal and ventral tiers of the substantia nigra pars compacta harbor various types of neurons the axons of which branch not only within the striatum but also in other major components of the basal ganglia. This paper reviews two of the major features of the nigrostriatal pathway, its axonal collateralization, and compartmental specificity, as revealed by single-axon labeling experiments in rodents and immunocytological analysis of human postmortem tissue.
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