This paper describes the development of Connectome-seq, a high-throughput technology designed to map neuronal connectivity at the resolution of individual synapses. By utilizing engineered viral vectors and RNA barcoding, the method labels connected neurons with unique genetic identifiers that can be read through single-cell sequencing. Unlike traditional imaging techniques that struggle with large brain volumes, this approach identifies circuits by isolating synaptosomes—physical structures containing both pre- and postsynaptic material—to match paired barcodes. The researchers successfully validated the platform in the mouse pontocerebellar circuit, demonstrating its ability to reveal molecular markers of specific connections. Ultimately, this tool provides a scalable way to integrate gene expression data with structural wiring diagrams to better understand complex brain functions.

References:

• Chen D, Isakova A, Wan Z, et al. Connectome-seq: high-throughput mapping of neuronal connectivity at single-synapse resolution via barcode sequencing[J]. Nature Methods, 2026: 1-16.