Heterogeneous distribution of D₁, D₂ and D₅ receptor mRNAs in monkey striatum

The primate striatum has a compartmental organization reflected both in the topography of its afferent projections and in the segregation of its morphologically similar but neurochemically distinct efferent neurons. Discretely projecting mesostriatal neurons release dopamine (DA) which modulates the responses of striatal neurons to other afferent inputs. Multiple DA receptor (DAR) subtypes have been cloned and characterized and mapping their cellular expression is crucial for understanding the influence of DA on striatal function. We report the distribution of mRNAs for D₁, D₂ and D₅ DAR subtypes (D₁R, D₂R and D₅R) in the striatum of cynomolgus monkeys (Macaca fascicularis) studied by in situ hybridization histochemistry (ISH) using monkey-specific cRNA probes. Adjacent sections were stained for calbindin immunoreactivity to distinguish striosomal and matrix compartments for comparison with the patterns obtained with ISH. In the caudate nucleus, D₁R mRNA was concentrated in calbindin-poor striosomes where dense grain clusters were seen overlying the majority of medium-sized neurons (diameter ∼ 15 μm). D₁R mRNA localization was relatively homogeneous in the putamen. By contrast, the distributions of D₂R and D₅R mRNAs showed no clear preference for the striosomal or matrix compartments of either caudate nucleus or putamen. In the ventral striatum (nucleus accumbens, olfactory tubercle and ventral portions of caudate nucleus and putamen), expression of D₁R and D₂R mRNA was sparse relative to dorsal striatum, while D₅R mRNA expression was roughly equal in ventral and dorsal striatum. Circumscribed zones of hybridization associated with islands of tightly packed small cells occurred with all three DAR mRNA subtypes in the ventral striatum. Large, putative cholinergic neurons which were seen in both the striatum and the adjacent basal forebrain, hybridized strongly with D₂R and D₅R cRNA probes but not with the D₁R probe. The different yet partially overlapping regional and cellular expressions of D₁R, D₂R and D₅R mRNAs suggest that the corresponding receptor subtypes subserve distinct functions in striatal neuronal processing.