Functional domains in dorsal striatum of the nonhuman primate are defined by the dynamic behavior of dopamine

Abstract

The dorsal striatum comprises a continuum of distinct functional domains, limbic, associative, and sensorimotor. In the primate it exclusively subdivides further into two nuclei, the putamen and caudate. Dopamine (DA) transmission is differentially affected between these nuclei in neurodegenerative diseases such as Parkinson's and by psychostimulants such as cocaine. Because rodent systems can offer only limited insight into DA systems of the human brain, a fuller appreciation of DA transmission and its role in dysfunction requires direct study in primates. DA behavior was explored in the major functional domains of the caudate nucleus and compared with the putamen, using fast-scan cyclic voltammetry in striatal sections from the marmoset (Callithrix jacchus). There was domain-specific variation in extracellular DA transients [i.e., concentration ([DA]o) released by a single stimulus and the rate maximum of DA uptake, Vmax]. Across nuclei, functional rather than anatomical regions were differentiated by these dynamics. The largest, fastest DA transients were at motor-associated loci. Evoked [DA]o at physiological frequencies was differently frequency-sensitive between functional domains but not between anatomical nuclei. In contrast, presynaptic depression was not an index of regional differentiation, recovering with similar kinetics at all loci. Within a given functional domain of dorsal striatum, the dynamics of DA release and uptake are similar for the putamen and the caudate nucleus. Conversely, distinct functional domains are defined by these DA dynamics, in a manner more marked in primates than in rodents. These data from the primate brain highlight differences in DA availability that may be central to DA function and dysfunction in the human.