The striatum is an essential structure influencing behavioral action selection in processes relevant to reward and motivation. Abnormalities in striatal function are associated with several psychiatric and neurological disorders, including addiction, depression, schizophrenia, Parkinson's disease, and Huntington's disease (Kreitzer and Malenka, 2008). The striatum comprises the dorsal striatum, which regulates motor output and decision-making, and the ventral striatum, which predominantly regulates reward and hedonic states. Both regions receive excitatory inputs from cortical and thalamic regions, as well as receiving dense innervation from midbrain dopaminergic nuclei.

The striatum lacks glutamatergic neurons; instead, nearly all striatal neurons are GABAergic. These GABAergic neurons include a large population of principal projection neurons called medium spiny neurons (MSNs) and a much smaller population comprising multiple classes of interneurons (Kreitzer and Malenka, 2008). MSNs can be further divided by their expression of Type 1 (D1) or Type 2 (D2) dopamine receptors. These classes play largely divergent roles in motor control and goal-directed behavior. Whereas D1 MSNs have primarily been shown to promote motor output and goal-directed behavior, D2 MSNs have been shown to inhibit these behaviors (Kravitz et al., 2010, 2012; Durieux et al., 2012; Freeze et al., 2013). These opposing behavioral functions are attributed to the distinct projection targets of D1 and D2 MSNs within the basal ganglia. Dorsal striatal D1 MSNs directly disinhibit the dopaminergic ventral mesencephalon to promote motivation, whereas D2 MSNs indirectly inhibit the dopaminergic mesencephalon by way of the globus pallidus to reduce motivation. With respect to their projections to basal ganglia nuclei, the dorsal and ventral striatum have traditionally been considered anatomically analogous; D1 MSNs in the ventral striatum project directly to the ventral mesencephalon, and D2 MSNs in the ventral striatum project indirectly to the ventral mesencephalon by way of the ventral pallidum (Kreitzer and Malenka, 2008). However, recent evidence suggests that, unlike the dorsal striatum, ventral striatal MSN output projections do not segregate exclusively based on D1/D2 subtype or by the direct/indirect pathway. For example, approximately half of the neurons in the ventral pallidum receive input from ventral striatal D1 MSNs, suggesting that there is some anatomical overlap in D1 and D2 MSN projection targets (Kupchik et al., 2015). In addition, the ventral pallidum itself projects to multiple limbic and cortical regions in addition to the ventral mesencephalon (Smith et al., 2009). These findings bring into question whether the traditional anatomical, and more importantly, behavioral distinctions between D1 and D2 MSNs are appropriate for the ventral striatum.