A new brain mapping method, called MAPseq (Multiplexed Analysis of Projections by Sequencing) can trace the axonal projections of individual neurons using sequencing technology rather than microscopy. Researchers led by Anthony Zador at Cold Spring Harbor Laboratory in New York have developed a method to label neurons of interest in the brain with an engineered virus that contains a large library of unique, 30-nucleotide RNA sequences, which serve as a barcode. Barcode mRNA is transported along axonal projections and accumulates at the axon terminals. Next, the RNA from target regions of interest is extracted and sequenced, and the RNA barcodes are used to trace the axons back to their neuron of origin. This novel technique can help decipher brain circuitry at the single neuron resolution, unlike batch labeling methods, and may in the future yield insights about how these circuits are affected by disease. Proof-of-principle experiments were recently published in the September 7 Neuron.
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Kebschull JM, Garcia da Silva P, Reid AP, Peikon ID, Albeanu DF, Zador AM. High-Throughput Mapping of Single-Neuron Projections by Sequencing of Barcoded RNA. Neuron. 2016 Sep 7;91(5):975-87. Epub 2016 Aug 18. [Pubmed].