Recent developments in cell-type-specific tools to investigate neural circuits have allowed researchers to evaluate the role of D1-MSNs and D2-MSNs in the expression of motivated and addictive behavior. As expected from the canonical circuitry, NAc D1-MSN activation promotes drug-seeking behavior while D2-MSNs had an inhibitory effect. However, other studies have shown that it is the input to the VP, rather than to the VM, which promotes reinstatement of drug-seeking behavior after withdrawal and that the VP itself, unlike its dorsal counterpart the globus pallidus, directly inhibits the thalamus (Root et al, 2015). Thus, the classic circuitry of the reward system was questioned.

In a recent study (Kupchik et al, 2015), we provided the first definitive evidence that the direct and indirect pathways of the NAc are not coded by MSN cell types (Figure 1). Using optogenetics in transgenic mice combined with neural tracing tools we showed that D1-MSNs comprise a significant portion of the classical indirect pathway by synapsing on VP neurons that project to the VM. Conversely, we showed that NAc D2-MSNs target VP neurons that innervate the thalamus directly. Thus, these D2-MSNs make a direct pathway through the VP that disinhibits the thalamus. These findings are not restricted to the ventral striatum as other emerging studies have observed similar results in the dorsal striatum (Cazorla et al, 2014; Saunders et al, 2015).

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