Structural and molecular heterogeneity of calretinin‐expressing interneurons in the rodent and primate striatum
In both mice and rats, striatal CR+ interneurons can be separated into at least two groups based on cell body size (Petryszyn, Beaulieu, Parent, & Parent, 2014; Rymar, Sasseville, Luk, & Sadikot, 2004). In the mouse, small‐sized CR+ interneurons are more common in the rostral and dorsal parts of striatum (Petryszyn et al., 2014). Many CR+ interneurons in these areas of rodent striatum express the transcription factor SP8 (Wei et al., 2011) or the CBP secretagogin (Kosaka, Yasuda, & Kosaka, 2017), but whether the expression of these molecules correlates with soma size in these areas has not been investigated. In the monkey striatum, three populations of CR+ interneurons have also been described based on their structural properties (Parent, Fortin, Cote, & Cicchetti, 1996; Petryszyn et al., 2014). In order of decreasing prevalence, there is a group comprised of “medium‐sized” (10–20 μm in somatic diameter) CR+ cells (Wu & Parent, 2000), a group of “small‐sized” (10–12 μm) cells, and a group of “large‐sized” (25–40 μm) cells. Although there is no evidence of molecular divergence of small‐ and medium‐sized interneurons in primates, the large‐sized CR+ interneurons often co‐express choline acetyltransferase (ChAT) (Cicchetti, Beach, & Parent, 1998; Petryszyn et al., 2014). This represents an important difference between the primate and rodent striatum, as neither mice nor rats have interneurons co‐expressing ChAT and CR (Figueredo‐Cardenas, Medina, & Reiner, 1996; Petryszyn et al., 2014). Without this molecular correlate of large CR+ interneurons, it is unclear whether the rodent striatum has two (Petryszyn, Parent, & Parent, 2017) or three (Tepper et al., 2010) classes of CR+ interneuron.
In both rodents and primates, a more detailed quantification of the molecular identity of CR+ neurons with different structural properties is needed to better differentiate subtypes of CR+ interneuron. Such a characterization could also provide greater understanding of the role of these interneurons in patients with Huntington's disease and Tourette syndrome, where there is a preferential loss of large‐sized striatal CR+ interneurons and relative sparing of the medium‐sized cells (Cicchetti et al., 2000; Kataoka et al., 2010). Using a combination of immunohistochemistry and stereological cell counting, we demonstrate that the selective expression of Scgn, as well as the transcription factors SP8 and Lhx7, within the CR+ interneuron population can be used to identify three cell “types” that can be distinguished from one another on the basis of their structural properties and distribution within the dorsal striatum of the rat and mouse.