Over 95% of the cells within the NAc are medium-sized spiny neurons (MSNs), which receive excitatory inputs from four major brain regions, the prefrontal cortex, the ventral subiculum of the hippocampus, the basolateral amygdala and the thalamus (Sesack and Grace, 2010). Surprisingly, little is known about potential differences in the synaptic properties of these different inputs and whether these different synapses are modified in an identical fashion by drugs of abuse during the transition to addiction. This is an important topic given that these different inputs must serve different behavioral functions. Another critical feature of NAc MSNs is that as in the dorsal striatum, they can be divided into two major classes, direct pathway and indirect pathway MSNs with the former primarily expressing D1 DA receptors and the latter D2 DA receptors (Kreitzer and Malenka, 2008). Finally, the NAc contains two subregions known as the core and the shell, which differ in their anatomical connectivity and their presumptive functions. The complexity of NAc circuitry generated by its multiple different inputs, different cell types and different subregions provides a major challenge
