Sex differences in the distribution and density of regulatory interneurons in the striatum

Abstract

Dysfunction of the cortico-basal circuitry – including its primary input nucleus, the striatum – contributes to neuropsychiatric disorders, including autism and Tourette Syndrome (TS). These conditions show marked sexual dimorphism, occurring more often in males than in females. Regulatory interneurons, including cholinergic interneurons (CINs) and parvalbumin-expressing GABAergic fast spiking interneurons (FSIs), are implicated in human neuropsychiatric disorders such as TS, and ablation of these interneurons produces relevant behavioral pathology in male mice, but not in females. Here we investigate sexual dimorphism in the density and distribution of striatal interneurons, using stereological quantification of CINs, FSIs, and somatostatin-expressing (SOM) GABAergic interneurons in the dorsal and ventral striatum in male and female mice. Males have a higher density of CINs than females, specifically in the dorsal striatum; females have equal distribution between dorsal and ventral striatum. FSIs showed similar effects, with a greater dorsal-ventral density gradient in males than in females. SOM interneurons were denser in the ventral than in the dorsal striatum, with no sexual dimorphism. These sex differences in the density and distribution of FSIs and CINs suggest a potential source of the sexual dimorphism seen in TS and autism spectrum disorder.