Imaging Activity-Dependent Gene Expression in Neurons: RNA-Tagging Technologies

Experience-driven modulation of gene expression in a neuronal circuit underlies information processing and storage in the brain. Since mRNAs are the blueprints for proteins, determining how neuronal activity influences mRNA processing to modify the neuronal proteome is crucial to our understanding of brain function. Several methodologies for measuring RNAs in neuronal populations exist; however, the ability to visualize mRNAs across space and time provides new perspectives into the dynamics of transcriptional and post-transcriptional events in real time. This chapter highlights the latest technological developments toward high-resolution imaging of gene dynamics ex vivo and in vivo by fluorescent tagging of endogenous mRNAs. We review the new insights into activity-dependent transcriptional regulation that these technologies reveal, focusing on excitation–transcription coupling mechanisms and how different inputs/signaling transduce transcriptional programs to impact neuronal plasticity. We discuss the technological challenges of visualizing RNAs and the improvements needed to apply fluorescent tagging of RNAs in vivo. High-definition imaging of RNA regulation in neurons can be an important tool to establish fundamental relationships between gene dynamics and experience-driven brain adaptations.