An example of the types of studies that will advance our understanding of the neural circuit adaptations that underlie addiction comes from experiments using BAC transgenic mice in which specific subpopulations of cells can be labeled with fluorescent markers (Gong et al., 2003). As mentioned above, NAc MSNs are not homogeneous but, like MSNs in the dorsal striatum, can be divided into two major subpopulations (Kreitzer and Malenka, 2008; Sesack and Grace, 2010; Gertler et al., 2008). Direct pathway MSNs express D1 DA receptors and project directly to midbrain DA areas whereas indirect pathway MSNs expresses D2 DA receptors and project to the ventral pallidum. In the dorsal striatum, there is growing evidence that these two subpopulations of MSNs exhibit different physiological and synaptic properties including different forms of synaptic plasticity (Kreitzer and Malenka, 2008; Shen et al., 2008). Indeed, independent manipulation of the activity of direct and indirect pathway MSNs in the dorsal striatum directly demonstrated that they participate in distinct circuits that mediate dramatically different behaviors (Hikida et al., 2010; Kravitz et al., 2010).
