Striatal Neurons Expressing D1 and D2 Receptors are Morphologically Distinct and Differently Affected by Dopamine Denervation in Mice

<jats:title>Abstract</jats:title><jats:p>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<jats:sub>1</jats:sub> or D<jats:sub>2</jats:sub> dopamine receptor. Consequences on MSNs expressing both receptors (D<jats:sub>1</jats:sub>/D<jats:sub>2</jats:sub> MSNs) are currently unknown. We looked for changes induced by dopamine denervation in the density, regional distribution and morphological features of D<jats:sub>1</jats:sub>/D<jats:sub>2</jats:sub> MSNs, by comparing 6-OHDA-lesioned double BAC transgenic mice (<jats:italic>Drd1a</jats:italic>-tdTomato/<jats:italic>Drd2</jats:italic>-EGFP) to sham-lesioned animals. D<jats:sub>1</jats:sub>/D<jats:sub>2</jats:sub> 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<jats:sub>1</jats:sub> and D<jats:sub>2</jats:sub> MSNs, D<jats:sub>1</jats:sub>/D<jats:sub>2</jats:sub> 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<jats:sub>1</jats:sub>/D<jats:sub>2</jats:sub> MSNs, but also of D<jats:sub>1</jats:sub> and D<jats:sub>2</jats:sub> MSNs, is significantly reduced in 6-OHDA-lesioned mice. In contrast to D<jats:sub>1</jats:sub> and D<jats:sub>2</jats:sub> MSNs, the extent of dendritic arborization of D<jats:sub>1</jats:sub>/D<jats:sub>2</jats:sub> MSNs appears unaltered in 6-OHDA-lesioned mice. Our data indicate that D<jats:sub>1</jats:sub>/D<jats:sub>2</jats:sub> MSNs in the mouse striatum form a distinct neuronal population that is affected differently by dopamine deafferentation that characterizes Parkinson’s disease.</jats:p>