, 2009). The vast majority of these cells are PV+ FS interneurons and calbindin (CB)-expressing LTS interneurons but only rarely CR+ interneurons; it is estimated that up to 60% of PV+, 25% of CB+, and <10% of CR+ interneurons express D1 receptors (Le Moine and Gaspar, 1998). The fraction of interneurons expressing D1-like receptors may be larger, as D5 receptors complement the expression pattern of D1 receptors, labeling mostly

CR+ interneurons, and less so PV+ interneurons (Glausier et al., 2009). By contrast, D2 receptors distribute to a comparatively smaller fraction of cortical GABAergic interneurons: only 5%–17% of interneurons contain D2 receptor mRNA (Santana et al., 2009), the majority of which consist of PV+ interneurons (Le Moine and Gaspar, 1998). Although D3 and D4

receptors GW572016 may complement the expression of D2 receptors in cortical interneurons, their overall distribution is limited (Khan et al., 1998), indicating that D2-like receptors are unlikely to distribute to a large proportion of GABAergic Navitoclax interneurons. Transgenic mice have the potential to help identify cortical cells with transcriptionally active DA receptor genes. However, currently available transgenic lines for D1 and D2 receptors were selected based on the fidelity of transgene expression in striatal neurons (Valjent et al., 2009). Comparatively little is known in cortex regarding the penetrance and specificity of these transgenes in D1 and D2 receptor-expressing neurons. A recent study by Zhang

et al. (2010) determined that Drd2-EGFP/Drd1a-tdTomato BAC transgenic mice express EGFP in over 90% of PFC pyramidal neurons and tdTomato in 16%–25% of pyramidal cells, most of which coexpress EGFP, without any region or layer-specific differences. This distribution stands in stark contrast the to that described previously ( Bentivoglio and Morelli, 2005). In another recent study ( Gee et al., 2012), PFC pyramidal neurons identified in Drd2-EGFP and Drd2-Cre BAC transgenic mice were found to project to thalamus but not contralateral cortex, unlike previous descriptions using in situ hybridization ( Gaspar et al., 1995). These discrepancies probably speak to the weaknesses of both histological and transgenic approaches. BAC transgenes are generated by nonspecific integration into the target genome and are not immune to positional effects, requiring phenotypic characterization of several transgenic lines before identifying the ones that most closely recapitulate endogenous gene expression patterns. Moreover, transgenic reporter and effector proteins are not subject to the same posttranscriptional and homeostatic regulatory mechanisms that control GPCR expression and may therefore highlight cells that do not functionally detect DA under normal conditions. Conversely, low-abundance GPCR transcripts may be functionally relevant but below the detection limit of conventional histological methods.