Ablation of the D1 Dopamine Receptor Alters the Migration and the Cortical Distribution of MGE-Derived Inhibitory...

Others have shown that dopamine receptors regulate the migration of GABAergic cortical interneurons (cINs) to the developing cortex. Given the strong expression of Drd1, the gene encoding the D1 dopamine receptor (D1R) in the developing cortex, we examined here the role of D1R in the cortical migration of interneurons born in the medial ganglionic eminence (MGE). Embryos of transgenic mice expressing cytoplasmic GFP under the control of the Drd1 promoter exhibited strong GFP expression in cells located in the deep cortical layers, including the subplate, and in the marginal zone. In co-culture experiments aimed at characterizing the effect of selective Drd1 ablation either in interneurons or in cortical plate cells on the migratory behavior of interneurons, we identified a prominent pro-migratory non-cell autonomous effect of Drd1 ablation in the cortical substrate. To assess whether Drd1 ablation in cortical cells could influence the final interneuron distribution in vivo, we analyzed the cortical distribution of parvalbumin and somatostatin positive interneurons in the cortex of Drd1-CKO (Drd1-/- cortical cells, Drd1+/+ interneurons) mice. Wild type parvalbumin and somatostatin interneurons exhibited slight but significant density changes and alterations of latero-dorsal distribution compatible with the pro-migratory effect of Drd1-/- cortical cells. In Drd1-KO animals (Drd1-/- cortical cells and Drd1-/- interneurons), the distribution alterations of parvalbumin and somatostatin interneurons were reminiscent of those in Drd1-CKO mutants. We thus propose that D1R regulates in the cortex the motility and distribution of MGE-derived cINs by preponderant non-cell-autonomous mechanism.