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

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 and Steven A. McCarroll ()
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Arpiar Saunders: Harvard Medical School
Kee Wui Huang: Harvard Medical School
Cassandra Vondrak: Harvard Medical School
Christina Hughes: Harvard Medical School
Karina Smolyar: Harvard Medical School
Harsha Sen: Harvard Medical School
Adrienne C. Philson: Harvard Medical School
James Nemesh: Harvard Medical School
Alec Wysoker: Harvard Medical School
Seva Kashin: Harvard Medical School
Bernardo L. Sabatini: Harvard Medical School
Steven A. McCarroll: Harvard Medical School

Nature Communications, 2022, vol. 13, issue 1, 1-18

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

Date: 2022
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DOI: 10.1038/s41467-022-34334-1

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