Understanding the role of specific genes in diverse brain functions is a major challenge in neuroscience. To address this issue, we have optimized an in vivo transgene expression system based on the sindbis virus. In this chapter, we provide a detailed description of the cloning, production, and in vivo stereotaxic injection of sindbis viral particles expressing proteins of interest. As an example, we describe how this technique can be used to identify the roles of the transcription factor, cAMP-responsive-element binding protein, in the regulation of neuronal plasticity and memory formation.