Jung_2000_Neurosci_97_495

The present study used mice deficient for dopamine D(2) and D(3) receptors to test whether the expression of these two members of the D(2) class of receptors is essential for the normal expression of three markers that characterize the neurochemical differentiation of the striatum: the calcium-binding protein calbindin, tyrosine hydroxylase and acetylcholinesterase. Results from these experiments revealed that the expression of striatal tyrosine hydroxylase (the rate-limiting enzyme of dopamine synthesis) and acetylcholinesterase is unaffected even by the combined knockout of D(2) and D(3) receptors. However, D(2) and D(3) receptor knockouts differently affect the striatal expression of calbindin-D(28k) immunoreactivity. Prominent changes in the cellular distribution of calbindin are detected in striatal neurons of D(2) mutant mice. Whereas calbindin immunolabeling of wild-type neurons is prominent in the nuclei and the cytoplasm of medium spiny neurons, in D(2) mutant mice, calbindin immunoreactivity is concentrated exclusively in the cytoplasmic rim of these neurons. Such changes in the cellular distribution of calbindin expression are not detected in mice lacking D(3) receptors. In these mutants, however, a lesser density of calbindin-immunoreactive neuropil is detected in the ventral portions of the striatum, i.e. in regions in which D(3) receptors are thought to be expressed at highest levels. Mice lacking both D(2) and D(3) receptors show both phenotypes. The altered cellular distribution of calbindin in D(2) mutants is likely to have functional consequences for some of the Ca(2+)-mediated cellular functions. The topography of the decreased density of striatal calbindin immunorectivity in D(3) mutants suggests a role for D(3) receptors in supporting the expression of striatal calbindin. The observation that mice lacking both D(2) and D(3) receptors show a combination of the D(2) and D(3) mutant phenotypes indicates that each of the different phenotypes detected in the single mutants is indeed related to the lack of the two different D(2)-like receptor subtypes.