Deletion of GAD67 in dopamine receptor-1 expressing cells causes specific motor deficits.

The medium spiny neurons (MSNs), which comprise the direct and indirect output pathways from the striatum, use gamma-aminobutyric acid (GABA) as their major fact-acting neurotransmitter. We generated mice carrying a conditional allele of the Gad1 gene, which encodes GAD67, one of the two enzymes responsible for GABA biosynthesis, and bred them to mice expressing Cre recombinase at the dopamine D1 receptor locus (Drd1a) to selectively reduce GABA synthesis in the direct output pathway from the striatum. We show that these mice are deficient in some types of motor skills, but normal for others, suggesting a differential role for GABA release from D1 receptor-containing neurons.