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

The two main types of corticostriatal neurons are those that project only intratelencephalically (IT-type), the intrastriatal terminals of which are 0.41 microm 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 microm 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 microm in mean diameter, whereas those making asymmetric axospinous contact with striatopallidal neurons were 0.69 microm. Second, we preferentially immunolabeled striatonigral neurons for D1 dopamine receptors or striatopallidal neurons for D2 dopamine receptors and found that axospinous terminals had a smaller mean size (0.45 microm) on D1+ spines than on D2+ spines (0.61 microm). Finally, we combined selective BDA labeling of IT-type or PT-type terminals with immunolabeling for D1 or D2, and found that IT-type terminals were twice as common as PT-type on D1+ spines, whereas PT-type terminals were four times as common as IT-type on D2+ 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.