Dopamine Differentially Modulates the Excitability of Striatal Neurons of the Direct and Indirect Pathways in Lamprey

The functions of the basal ganglia are critically dependent on dopamine. In mammals, dopamine differentially modulates the excitability of the direct and indirect striatal projection neurons, and these populations selectively express dopamine D-1 and D-2 receptors, respectively. Although the detailed organization of the basal ganglia is conserved throughout the vertebrate phylum, it was unknown whether the differential dopamine modulation of the direct and indirect pathways is present in non-mammalian species. We aim here to determine whether the receptor expression and opposing dopaminergic modulation of the direct and indirect pathways is present in one of the phylogenetically oldest vertebrates, the river lamprey. Using in situ hybridization and patch-clamp recordings, we show that D-1 receptors are almost exclusively expressed in the striatal neurons projecting directly to the homolog of the substantia nigra pars reticulata. In addition, the majority of striatal neurons projecting to the homolog of the globus pallidus interna/globus pallidus externa express D-1 or D-2 receptors. As in mammals, application of dopamine receptor agonists differentially modulates the excitability of these neurons, increasing the excitability of the D-1-expressing neurons and decreasing the excitability of D-2-expressing neurons. Our results suggest that the segregated expression of the D-1 and D-2 receptors in the direct and indirect striatal projection neurons has been conserved across the vertebrate phylum. Because dopamine receptor agonists differentially modulate these pathways, increasing the excitability of the direct pathway and decreasing the excitability of the indirect pathway, this organization may be conserved as a mechanism that biases the networks toward action selection.