The Neostriatal Mosaic: Compartmental Organization of Mesostriatal Systems

Abstract

The compartmental organization of the dopaminergic and nondopaminergic containing projections from the midbrain to the striatum was examined in the rat. In order to determine the relative inputs from various midbrain neurons to either of the striatal “patch” or “matrix” compartments methods were combined to label mesostriatal afferents with the anterograde axonal tracer PHA-L and to compare their distribution relative to autoradiographically localized mu-opiate receptors in patches. A non-dopaminergic nigrostriatal projection was identified to the striatal matrix compartment. Two dopaminergic (DA) mesostriatal systems were identified. One system, directed to the striatal matrix compartment, was shown to arise from neurons in the ventral tegmental area (A10 DA cell group), the dorsal tier of the substantia nigra pars compacta (dorsal A9 DA cell group) and the retrorubral area (A8 DA cell group). The other system, directed to the striatal patch compartment, was shown to arise from neurons in the ventral tier of the substantia nigra pars compacta (ventral A9 DA cell group) and from DA cells in the substantia nigra pars reticulata. The asynchronous development of the “patch” and “matrix” mesostriatal systems provides a means of further characterization. Injections of the neurotoxin 6-hydroxydopamine into the striatum on the day of birth (P0), when the patch system is in place but prior to the ingrowth of the matrix dopaminergic system, resulted in the select and long-lasting depletion of the patch dopaminergic system. Such lesions provided a clear delineation of dopaminergic neurons projecting to the striatal matrix, as they were selectively spared by the neonatal lesions. First, the distribution of these neurons matched that deduced from the PHA-L tracing studies. Second, the dendrites of matrix directed neurons are distributed amongst other DA neurons, whereas those DA neurons which project to the patches possess dendrites which are distributed into the non-dopaminergic parts of the substantia nigra pars reticulata. Third, a brain calcium binding protein (calbindin D28kD or CaBP) is expressed by those dopaminergic neurons which project to the striatal matrix and not by those which project to the patches.