Understanding how molecular signaling pathways participate in behavioral responses requires determining precisely in which neuronal populations they are activated. The recent development of bacterial artificial chromosome (BAC) transgenic mice expressing a variety of reporters, epitope tagged-proteins or Cre recombinase driven by specific promoters, is a significant step forward in this direction. These mice help overcome the limitations of traditional approaches that examine an average of signaling events occurring in mixed populations of cells. Here, we review how recent studies using such tools have revisited the regulation of striatal signaling pathways, demonstrating the striking segregation between neurons expressing dopamine D1 and D2 receptors and significantly extending our overall knowledge of striatal neurons. Thus, BAC transgenic mice are changing the way to conceive experiments and provide an opportunity to fill the gaps between molecular and systems neurosciences.