Chemical anatomy of primate basal ganglia

This paper provides an overview of the anatomical and functional organization of the most prominent chemospecific neuronal systems that compose the basal ganglia in primates. Emphasis is placed on the heterogeneity and diversity of small-molecule transmitters, neuroactive peptides and proteins used by basal ganglia neurons. Dopaminergic, serotoninergic and cholinergic neuronal systems are shown to comprise multiple subsystems organized according to highly specific patterns. These subsystems differentially regulate gene expression of several neuroactive peptides, including tachykinins, enkephalins, dynorphin, somatostatin, and neuropeptide Y, that are used by distinct subsets of basal ganglia neurons. Glutamatergic excitatory inputs establish distinct functional territories within the basal ganglia, and neurons in each of these territories act upon other brain neuronal systems through a GABAergic disinhibitory output mechanism. A striking complementary pattern of distribution of the calcium-binding proteins parvalbumin and calbindin D-28k is noted in all basal ganglia components. The limbic system-associated membrane protein (LAMP) is confined chiefly to basal ganglia sectors that are anatomically and functionally related to limbic system structures; these may serve as functional interfaces between the basal ganglia and the limbic system. The functional status of the various basal ganglia chemospecific systems in neurodegenerative diseases, such as Parkinson's disease and Huntington's chorea, is examined. It is concluded that these multiple transmitter-related systems cannot be analyzed separately as they form highly complex and interactive neuronal networks. These complexities should be taken into account to reach a better understanding of the functions of primate basal ganglia in health and disease.