The organization of midbrain projections to the ventral striatum in the primate

Because the dopaminergic neurons of the midbrain form a continuum, boundaries between the ventral tegmental area, substantia nigra pars compacta, and retrorubral area are difficult to distinguish in the primate. Therefore, dopaminergic neurons have been subdivided into more readily discernible dorsal and ventral tiers. The projections from these dorsal and ventral tier neurons of the ventral mesencephalon to the ventral striatum were labeled by injections of horseradish peroxidase conjugated to wheatgerm agglutinin and Lucifer Yellow conjugated to dextran amines into different regions of the nucleus accumbens, the ventral caudate nucleus, and the rostral, ventral putamen in the primate. Neurons projecting to the ventral striatum are not topographically organized in the ventral mesencephalon. Retrogradely labeled neurons are found in the medial densocellular zone of the ventral tier following injections into all regions of the ventral striatum except the ventromedial shell region of the nucleus accumbens. These medial nigral neurons have diverging projections throughout the mediolateral extent of the ventral striatum. In addition, neurons of the dorsal tier project to all ventral striatal regions examined. Notably, neurons projecting to the shell region of the nucleus accumbens are limited to the dorsal tier, throughout the rostrocaudal extent of the substantia nigra. Both dorsal and ventral tier neurons innervate the ventral striatum. Not only do neurons of the ventral tegmental area project to the ventral striatum, but also many of the pars compacta. The projections to the shell region of the nucleus accumbens are more restricted, suggesting that the dopaminergic regulation of this accumbens subterritory is distinct from the rest of the ventral striatum.