The main olfactory bulb (MOB) integrates information from sensory neurons in the main olfactory epithelium and targets downstream (sub)cortical nuclei via two projection neuron populations, i.e., mitral and tufted cells. However, reliable tools to selectively target either of the two neuron types are currently lacking.
Recombinant adeno-associated viruses (rAAVs) have become a powerful tool for unraveling brain connectivity because of their efficiency, low cytotoxicity, and robust transduction. With rAAVs, cell type-specific transduction efficiency depends on various factors, such as viral volume, titer, and serotype. Here, we set out to identify rAAVs best suited for studying mitral and / or tufted cell projections in the main olfactory system. To this end, we compared transduction patterns of different anterograde rAAV serotypes after stereotactic MOB injections in transgenic Tbx21-Cre mice, a driver line that provides genetic access to olfactory bulb projection neurons. We established an intact brain preparation that enables comprehensive histological analysis of entire circuits via confocal imaging at cellular resolution.
Our main findings reveal that, although rAAV serotype impacts transduction, other factors such as genomic design, play a crucial role in determining the cell-type specificity of rAAV transduction. Future investigations aim to develop reliable experimental tools that selectively target long-range projecting MOB mitral cells.