Neuroscientists propose a revolutionary DNA-based approach to map wiring of the whole brain

A team of neuroscientists have proposed a new and potentially revolutionary way of obtaining a neuronal connectivity map (the “connectome”) of the whole brain of the mouse. The details are set forth in an essay published October 23 in the open-access journal PLOS Biology.

The team, led by Professor Anthony Zador, Ph.D., of Cold Spring Harbor Laboratory, aims to provide a comprehensive account of neural connectivity. At present the only method for obtaining this information with high precision relies on examining individual cell-to-cell contacts (synapses) in electron microscopes. But such methods are slow, expensive and labor-intensive.

Zador and colleagues instead propose to exploit high-throughput DNA sequencing to probe the connectivity of neural circuits at the resolution of single neurons.

“Our method renders the connectivity problem in a format in which the data are readable by currently available high-throughput genome sequencing machines,” says Zador. “We propose to do this via a process we’re now developing, called BOINC: the barcoding of individual neuronal connections.”

The proposal comes at a time when a number of scientific teams in the U.S. are progressing in their efforts to map connections in the mammalian brain. These efforts use injections of tracer dyes or viruses to map neuronal connectivity at a “mesoscopic” scale—a mid-range resolution that makes it possible to follow neural fibers between brain regions.  Other groups are scaling up approaches based on electron microscopy.