FOLLOW THE mRNA: To determine where in the mouse brain individual neurons have axon terminals, researchers inject a library of viral vectors in the vicinity of cell bodies. The viruses contain plasmids each encoding a unique RNA barcode and a presynaptic protein called MAPP-nλ that will shuttle the barcoded mRNA to the ends of the axon. Typically, each cell takes up only one virus, giving that cell an RNA identifier. Dissecting brain regions and sequencing the RNAs reveals which cells project where.© GEORGE RETSECK
Several ambitious brain connectome projects are underway to diagram the wiring of animals’ most complicated organ. For the most part, neural cartographers rely on microscopy, but tracing numerous projections across the large volumes of the brain is “extremely painstaking and slow,” says Thomas Mrsic-Flogel of the University of Basel.
Inspired by recent advances in sequencing technology, Tony Zador of Cold Spring Harbor Laboratory had an idea: “If there was a way to convert the mapping problem into one of sequencing, it would be a [big] win in terms of throughput and cost.” Now, he and his colleagues have done just that.
To map neurons by sequencing, Zador’s team injects a mixture of approximately 106 viruses—each bearing a genetic sequence encoding a unique mRNA barcode—into mouse ...
