Striatal Neurons Expressing D1 and D2 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.