Ascertaining cells’ synaptic connections and RNA expression simultaneously with barcoded rabies virus libraries

• DOI: 10.1038/s41467-022-34334-1
• Publication Date: 2022-11-16T11:05:57Z
• Authors: Arpiar Saunders; Kee Wui Huang; Cassandra Vondrak; Christina Hughes; Karina Smolyar; Harsha Sen; Adrienne C. Philson; James Nemesh; Alec Wysoker; Seva Kashin; Bernardo L. Sabatini; Steven A. McCarroll
• Keywords: Cell type

Abstract Brain function depends on synaptic connections between specific neuron types, yet systematic descriptions of networks and their molecular properties are not readily available. Here, we introduce SBARRO ( S ynaptic B arcode A nalysis by R etrograde abies Read O ut), a method that uses single-cell RNA sequencing to reveal directional, monosynaptic relationships based the paths barcoded rabies virus from its “starter” postsynaptic cell cell’s presynaptic partners. Thousands these partner can be ascertained in single experiment, alongside genome-wide RNAs. We use describe formed diverse mouse brain types vitro, finding different have with differences average size type composition. Patterns expression suggest functioning synapses critical for uptake. By tracking individual clones across cells, offers new opportunities map organization neural circuits.