Differential expression of D1 and D2 dopamine and m4 muscarinic acetylcholine receptor proteins in identified striatonigral neurons.

Large families of genetically distinct G-protein coupled receptor subtypes mediate dopamine's (D1-D5) and acetylcholine's effects (m1-m5). A functional balance of dopamine and acetylcholine may be based in part on the differential expression of receptor subtypes by distinct neuron subpopulations. The localization of the D1 and D2 receptors, the predominant dopamine receptors in neostriatum, to distinct subpopulations of striatal projection neurons has been controversial. In addition, m4 receptor localization to specific striatal projection neuron subpopulations is also at question. To determine whether rat striatonigral neurons differentially express D1, D2, and m4 receptor proteins, we combined immunocytochemistry by using receptor subtype specific antibodies and retrograde tracing with cholera toxin-colloidal gold. D1 and m4 receptor immunoreactivity was visualized in 95% and 92% of identified striatonigral neurons, respectively. By contrast, D2 receptor immunoreactivity was visualized in only 1% of these neurons. These findings support models of basal ganglia in which D1 and D2 receptors are segregated, as well as indicate that D1 and m4 are colocalized. These cellular distributions may be important substrates for the putative DA/ACh balance that is implicated in certain movement disorders.