Compartment‐specific changes in the density of choline and dopamine uptake sites and muscarinic and dopaminergic receptors during the development of the baboon striatum: A quantitative receptor autoradiographic study

Abstract

In the fetal and young primate neostriatum, cholinergic and dopaminergic markers show patches of high density surrounded by a lower‐density matrix. In the adult, the same markers display the opposite pattern, a lower density in striosomes, surrounded by a higher‐density matrix. In order to understand the developmental sequences leading to the adult compartmental organization of the primate neostriatum, a quantitative technique was used to study the ontogeny of pre‐ and postsynaptic components of cholinergic and dopaminergic neurons in baboon caudate nucleus and putamen. The development of specific uptake mechanisms for choline and dopamine and receptors was studied by means of quantitative autoradiography of the specific binding of [³H]‐hemicholinium‐3 ([³H]‐HC3) and [³H]‐mazindol ([³H]‐MAZ) to the choline and dopamine uptake systems, respectively. [³H]‐pirenzepine ([³H]‐PIR) was used to label M1 muscarinic receptors and [³H]‐spiroperidol ([³H]‐SPI) was used to label striatal dopamine D2 receptors. Serial sections were used for each ligand to determine the precise anatomical relationships between the binding patterns of the different markers. Our aim was to determine whether the adult striosomal distribution of the binding sites studied was due to (1) a selective decrease in patch/striosomal binding density or (2) a selective increase in matrix binding density. Our studies show that a postnatal decrease in the density of [³H]‐HC3 sites in the patch/striosomes and an increase in the matrix density of [³H]‐MAZ sites are the primary, but not the sole, changes in the compartmental distribution of these sites leading to the adult striosomal organization of the striatal cholinergic and dopaminergic innervation. D2 receptors follow the general developmental pattern of [³H]‐MAZ and [³H]‐HC3, changing their density of distribution in both compartments during the developmental period examined. In addition, M1 muscarinic receptors already display their adult pattern in the newborn baboon striatum, and therefore represent one of the first neurochemical markers to adopt its mature organization.