Spatial analysis reveals alterations of parvalbumin- and calbindin-positive local circuit neurons in the cerebral cortex of mutant mdx mice

The aim of the present study was to investigate the spatial organization of selected populations of local circuit neurons in the cerebral cortex of the mutant mdx mouse, an acknowledged model of Duchenne Muscular Dystrophy. To this purpose, we quantified and compared the distribution of parvalbumin- and calbindin-positive neurons in the motor, somatosensory, visual, and anterior cingulate cortices of wildtype and mdx mice. The methodological approach was based on generation of two-dimensional Voronoi polygons from digital charts of the cell populations visualized immunohistochemically. Polygon areas were then analyzed and the derived coefficients of variation were statistically compared. Using this strategy, we were able to reveal, in mdx mice, changes involving both the above populations of interneurons. These changes were evident in the motor and anterior cingulate cortices but not in the somatosensory and visual cortices. In addition, the changes of coefficients of variation were area-specific in the cortex of mdx mice. The values increased in the motor cortex and decreased in the anterior cingulate cortex with respect to the corresponding values of wild-type animals. The present findings point out widespread alterations in the mdx cortex involving also areas not primarily related to sensorimotor integration. In addition, we demonstrate that cortical alterations of the local circuit machinery are characterized in mdx mice by individual regional differences.