Evidence for differential cortical input to direct pathway versus indirect pathway striatal projection neurons in rats

The two main types of corticostriatal neurons are those that project only intratelencephalically (IT-type), the intrastriatal terminals of which are 0.41 mum in mean diameter, and those that send their main axon into pyramidal tract and have a collateral projection to striatum (PT-type), the intrastriatal terminals of which are 0.82 mum in mean diameter. We used three approaches to examine whether the two striatal projection neuron types (striatonigral direct pathway vs striatopallidal indirect pathway) differ in their input from IT-type and PT-type neurons. First, we retrogradely labeled one striatal projection neuron type or the other with biotinylated dextran amine (BDA)3000 molecular weight. We found that terminals making asymmetric axospinous contact with striatonigral neurons were 0.43 mum in mean diameter, whereas those making asymmetric axospinous contact with striatopallidal neurons were 0.69 mum. Second, we preferentially immunolabeled striatonigral neurons for D-1 dopamine receptors or striatopallidal neurons for D-2 dopamine receptors and found that axospinous terminals had a smaller mean size (0.45 mum) on D-1+ spines than on D-2+ spines (0.61 mum). Finally, we combined selective BDA labeling of IT-type or PT-type terminals with immunolabeling for D-1 or D-2, and found that IT-type terminals were twice as common as PT-type on D-1+ spines, whereas PT-type terminals were four times as common as IT-type on D-2+ spines. These various results suggest that striatonigral neurons preferentially receive input from IT-type cortical neurons, whereas striatopallidal neurons receive greater input from PT-type cortical neurons. This differential cortical connectivity may further the roles of the direct and indirect pathways in promoting desired movements and suppressing unwanted movements, respectively.