RT Journal Article SR Electronic T1 High-throughput mapping of single neuron projections by sequencing of barcoded RNA JF bioRxiv FD Cold Spring Harbor Laboratory SP 054312 DO 10.1101/054312 A1 Justus M Kebschull A1 Pedro Garcia da Silva A1 Ashlan P Reid A1 Ian D Peikon A1 Dinu F Albeanu A1 Anthony M Zador YR 2016 UL http://biorxiv.org/content/early/2016/05/20/054312.abstract AB Neurons transmit information to distant brain regions via long-range axonal projections. In the mouse, area-to-area connections have only been systematically mapped using bulk labeling techniques, which obscure the diverse projections of intermingled single neurons. Here we describe MAPseq (Multiplexed Analysis of Projections by Sequencing), a technique that can map the projections of thousands or even millions of single neurons by labeling large sets of neurons with random RNA sequences (“barcodes”). Axons are filled with barcode mRNA, each putative projection area is dissected, and the barcode mRNA is extracted and sequenced. Applying MAPseq to the locus coeruleus (LC), we find that individual LC neurons have preferred cortical targets. By recasting neuroanatomy, which is traditionally viewed as a problem of microscopy, as a problem of sequencing, MAPseq harnesses advances in sequencing technology to permit high-throughput interrogation of brain circuits.