Ekstrand, M.I. et al. Cell 157, 1230–1242 (2014).

The neuroanatomical description of circuitry in the mouse brain has advanced at a fast pace. However, the corresponding molecular characterization of these circuits is lagging behind. Ekstrand et al. now describe a method for profiling neurons presynaptic to a region of interest. The researchers created a mouse line that expresses a ribosomal protein fused to a GFP-specific camelid nanobody in all neurons. Then they injected a retrograde tracing virus into the region of interest. The virus encoded GFP, thereby delivering the nanobody epitope to presynaptic sites. Immunoprecipitation of the GFP-associated ribosomes, and subsequent RNA sequencing, uncovered mRNAs that are specifically enriched in neurons presynaptic to the injected brain region. With this method, marker genes for neurons projecting to regions of interest can be identified.