The density of calretinin striatal interneurons is decreased in 6-OHDA-lesioned mice

Interneurons play a significant role in the functional organization of the striatum and some of them display marked plastic changes in dopamine-depleted conditions. Here, we applied immunohistochemistry on brain sections from 6-hydroxydopamine (6-OHDA) mouse model of Parkinson’s disease and sham animals to characterize the regional distribution and the morphological and neurochemical changes of striatal interneurons expressing the calcium binding protein calretinin (CR). Two morphological subtypes of calretinin-immunostained (CR+) interneurons referred respectively as small and medium-sized CR+ interneurons were detected in 6-OHDA and sham-lesioned animals. The small cells (9-12 µm) prevail in the anterior and dorsal striatal regions; they stain intensely for CR and display a single slightly varicose and moderately arborized process. The medium-sized CR+ interneurons (15-20 µm) are slightly more numerous than the small CR+ cells and rather uniformly distributed within the striatum; they stain weakly for CR and display 2-3 long, slightly varicose and poorly branched dendrites. The density of medium CR+ interneurons is significantly decreased in the dopamine-depleted striatum (158 ± 15 neurons/mm3), when compared to sham animals (370 ± 41 neurons/mm3), whereas that of the small-sized CR+ interneurons is unchanged (174 ± 46 neurons/mm3 in 6-OHDA-lesioned striatum and 164 ± 22 neurons/mm3 in sham-lesioned striatum). The nucleus accumbens is populated only by medium-sized CR+ interneurons, which are distributed equally among the core and shell compartments and whose density is unaltered after dopamine denervation. Our results provide the first evidence that the medium-sized striatal interneurons expressing low level of CR are specifically targeted by dopamine denervation, while the small and intensely immunoreactive CR+ cells remain unaffected. These findings suggest that high expression of the calcium binding protein CR might protect striatal interneurons against an increase in intracellular calcium level that is believed to arise from altered glutamate corticostriatal transmission in Parkinson’s disease.