Synaptology of the nigrostriatal projection in relation to the compartmental organization of the neostriatum in the rat

Abstract

The patch-matrix organization of the striatal complex, which is fundamental to the structural and functional organization of the basal ganglia, is characterized on the basis of both connections and neurochemistry. In order to determine whether differences in the connections and neurochemistry are reflected in differences in synaptic organization, we examined the synaptology of the dopaminergic nigrostriatal projection in the patch-matrix complex of the rat. Three approaches were used. First, deposits of the anterograde tracer, biotinylated dextran amine, were placed in the substantia nigra. Sections of perfuse-fixed neostriatum were then processed to reveal anterogradely-labelled nigrostriatal axons and calbindin-D28k immunoreactivity, a marker for the patch-matrix complex. Secondly, sections of perfuse-fixed neostriatum were immunolabelled to reveal both tyrosine hydroxylase, a marker for dopaminergic structures and calbindin-D28k. Labelled axons in the patches and the matrix were examined at both the light and the electron microscopic levels. Finally, in order to test for the presence of fixed GABA in sub-types of anterogradely-labelled terminals in the neostriatum, ultrathin sections were immunolabelled by the post-embedding immunogold method. Based on morphological analysis, anterogradely-labelled nigrostriatal axons were divided into two types (Type I and Type II). The density of tyrosine hydroxylase labelling in the neostriatum prevented the classification of immunolabelled nigrostriatal axons. The Type I anterogradely-labelled axons and tyrosine hydroxylase-positive axons were found both in the patches and in the matrix. They both formed symmetrical synapses with spines, dendrites and occasionally somata. The morphology, dimensions, type of synaptic specialization and the distribution of postsynaptic targets of axons labelled by both methods were similar in the patches and the matrix. The Type I anterogradely-labelled axons were immunonegative for GABA. The Type II anterogradely-labelled axons were GABA-immunopositive, were found only in the matrix and were only present in those animals in which retrograde labelling was observed in the globus pallidus, they are thus not part of the dopaminergic nigrostriatal projection. It is concluded that although the patch-directed and matrix-directed dopaminergic projections from the ventral mesencephalon arise from different populations of dopaminergic neurons, their innervation of neurons in the patches and matrix is similar. The anatomical substrate, and therefore probably also the mechanism, for dopaminergic modulation of the flow of cortical information through the striatal complex is essentially the same in patches and in the matrix sub-divisions of the striatal complex.