Basal ganglia and thalamic input from neurons located within the ventral tier cell cluster region of the substantia nigra pars compacta in the rat

Abstract

The most caudally located dopaminergic (DA) ventral tier neurons of the substantia nigra pars compacta (SNc) form typical cell clusters that are deeply embedded in the substantia nigra pars reticulata (SNr). Here we examine the efferent projections of 35 neurons located in the SNr region where these SNc cell clusters reside. The neuronal cell body was injected with biotinylated dextran amine so as to trace each complete axon in the sagittal or the coronal plane. Electrophysiological guidance guaranteed that the tracer was ejected among neurons displaying a typical SNc discharge pattern. Furthermore, double immunofluorescence and immunohistochemical labeling ensured that the tracer deposits were placed within the DA cell clusters. Three types of projection neurons occurred in the SNc ventral tier cell cluster region: type I neurons, projecting to basal ganglia; type II neurons, targeting both the basal ganglia and thalamus; and type III neurons, projecting only to the thalamus. The striatum was targeted by most of the type I and II neurons and the innervation reached both the striosome/subcallosal streak and matrix compartments. Many nigrostriatal fibers provided collaterals to the globus pallidus and, less frequently, to the subthalamic nucleus. At a thalamic level, type II and III neurons preferentially targeted the reticular, ventral posterolateral, and ventral medial nuclei. Our results reveal that the SNr region where DA ventral tier cell clusters reside harbors neurons projecting to the basal ganglia and/or the thalamus, thus suggesting that neurodegeneration of nigral neurons in Parkinson's disease might affect various extrastriatal basal ganglia structures and multiple thalamic nuclei.