Striatal Neurons Expressing D(1) and D(2) Receptors are Morphologically Distinct and Differently Affected by Dopamine Denervation in Mice

The loss of nigrostriatal dopamine neurons in Parkinson’s disease induces a reduction in the number of dendritic spines on medium spiny neurons (MSNs) of the striatum expressing D(1) or D(2) dopamine receptor. Consequences on MSNs expressing both receptors (D(1)/D(2) MSNs) are currently unknown. We looked for changes induced by dopamine denervation in the density, regional distribution and morphological features of D(1)/D(2) MSNs, by comparing 6-OHDA-lesioned double BAC transgenic mice (Drd1a-tdTomato/Drd2-EGFP) to sham-lesioned animals. D(1)/D(2) MSNs are uniformly distributed throughout the dorsal striatum (1.9% of MSNs). In contrast, they are heterogeneously distributed and more numerous in the ventral striatum (14.6% in the shell and 7.3% in the core). Compared to D(1) and D(2) MSNs, D(1)/D(2) MSNs are endowed with a smaller cell body and a less profusely arborized dendritic tree with less dendritic spines. The dendritic spine density of D(1)/D(2) MSNs, but also of D(1) and D(2) MSNs, is significantly reduced in 6-OHDA-lesioned mice. In contrast to D(1) and D(2) MSNs, the extent of dendritic arborization of D(1)/D(2) MSNs appears unaltered in 6-OHDA-lesioned mice. Our data indicate that D(1)/D(2) MSNs in the mouse striatum form a distinct neuronal population that is affected differently by dopamine deafferentation that characterizes Parkinson’s disease.