Organization of striatopallidal, striatonigral, and nigrostriatal projections in the macaque

Abstract

The topographic organization of neostriatal connections was investigated by axonal transport of horseradish peroxidase, tritiated amino acids, or mixtures of both injected into the neostriatum of macaque monkeys. Striatal projections to pallidum and substantia nigra and the origin of projections to striatum from cerebral cortex and substantia nigra were examined. All striatal injections gave rise to projections to external and internal pallidum and to substantia nigra. Injections in caudate nucleus and in putamen both gave rise to substantial projections to pallidum and to substantia nigra, and the ratio of pallidal and nigral projections was generally similar. The striatopallidal projection showed prominent arborizations at right angles to the striatofugal pathway traversing the pallidum, forming in this manner terminal fields consisting of multiple bands or discs within a broad segment of the pallidum. Thus separate but neighboring regions of striatum appeared to have overlapping pallidal projection territories. In broad terms, rostral striatum projects to rostral pallidum, caudal striatum to caudal pallidum, and dorsal and ventral striatum, respectively, to dorsal and ventral pallidum. Inner (medial) and outer (lateral) putamen showed only subtle differences in pallidal projection patterns. The striatonigral projection from each injected area of striatum formed a longitudinal band extending over the entire length of the substantia nigra, with scattered, dense terminal fields occupying portions of pars compacta as well as pars reticularis. Rostral striatum projected to medial nigra and caudal striatum to lateral nigra. Terminal fields from ventral striatum were located somewhat more dorsally in the substantia nigra than those from dorsal striatum. Neighboring but separate regions of striatum appeared to have overlapping nigral projection territories, especially in caudal nigra. The nigrostriatal neurons projecting to an injected area of striatum generally were located in the same longitudinal band of the substantia nigra as the corresponding striatonigral projection. Labeled pars compacta neurons were often surrounded by a dense, labeled striatonigral terminal field, suggesting the existence of a striato‐nigrostriatal loop. The rostromedial pars compacta contained labeled neuronal cell bodies in most cases, suggesting a widely divergent projection to striatum from this cell group. A slight tendency for preferential cell labeling rostrally in nigra with rostral striatal injection and caudally in nigra with caudal injections was noted. The preferred relationship of lateral nigra with caudal striatum and medial nigra with rostral striatum has implications for clinical expression of Parkinson's disease, which may vary with differential involvement of different nigral cell groups along the medial to lateral axis. In cases of mid‐putamen injection, corticostriatal neuronal perikarya were labeled in a broad frontoparietal zone encompassing most motor and somatosensory areas, while a case of rostral caudate injection displayed labeled cells in four separate cortical zones: cingulate gyrus, prefrontal cortex medial to the sulcus principalis, superior temporal gyrus, and medial temporal cortex (including entorhinal cortex). The projections to pallidum from injected areas of caudate nucleus and from injected areas of putamen showed little overlap. This finding is consistent with the concept of parallel, segregated pathways through the basal ganglia involving regions of neostriatum and pallidum controlled by association cortex and sensorimotor cortex. Neither the striatopallidal projection, nor the striatonigral projection, nor the origin of the nigrostriatal projection, nor the origin of the corticostriatal projection showed a simple point‐to‐point topographical organization, but rather ended in multiple terminal fields of complex organization or originated in multiple cell groups. This complex mode of connectional organization is shared by many other non‐sensory neuronal circuits in the central nervous system and is likely to be a key feature in their function.