June 03, 2012

Neuroscientists reach major milestone in whole-brain circuit mapping project

Neuroscientists at Cold Spring Harbor Laboratory (CSHL) reached an important milestone today, publicly releasing the first installment of data from the 500 terabytes so far collected in their pathbreaking project to construct the first whole-brain wiring diagram of a vertebrate brain, that of the mouse.

The data consist of gigapixel images (each close to 1 billion pixels) of whole-brain sections that can be zoomed to show individual neurons and their processes, providing a “virtual microscope.” The images are integrated with other data sources from the web, and are being made fully accessible to neuroscientists as well as interested members of the general public (

Composite image generated with Mouse Brain Architecture project data. Injections of two fluorescently marked (red and green) adeno-associated viral (AAV) tracers indicate neural pathways, superimposed upon a whole-brain image stained to reveal the protective sheathing around myelinated axons. Axonal paths leaving the injection site are seen, including horizontal ones crossing over to the other side of the brain along the Corpus Callosum.

Each sampled brain is represented in about 500 images, each image showing an optical section through a 20 micron-thick slice of brain tissue. A multi-resolution viewer permits users to journey through each brain from “front” to “back,” and thus enables them to follow the pathways taken through three-dimensional brain space by tracer-labeled neuronal pathways. The tracers were picked to follow neuronal inputs and outputs of given brain regions.

A number of features distinguish the “meso-scale” circuit project at CSHL. The 20-micron spacing between brain “slices” gives the CSHL results a particularly rich sense of three-dimensional depth and detail. The team’s use of four tracers including both classical tracer substances as well as neurotropic viruses (attenuated or disabled viruses that infect nerve cells), provides redundancy and helps control for differing efficacies of the different tracer substances. The images one sees on the MBA Project website begininng today provide hard data on actual neuronal processes – the “ground truth” of neuroanatomy, in Mitra’s words -- and do not rely on inferential methodologies such as functional MRI scans and diffusion tensor imaging to suggest areas in which connections occur. Finally, it is noteworthy that the slides generated by the project are being physically stored, to permit re-examination at a later date, using more refined imaging methods if necessary or as new methods become available.

“Our project is what I’d call a necessary first step in a much larger enterprise, that of understanding both structure and dynamics of the vertebrate, and ultimately, the human brain,” says Mitra. “While facile comparisons with Genome projects should be avoided, the data sets generated by the MBA and similar projects will provide a useful framework – not unlike a reference genome – on which we can ‘hang’ all kinds of neuroscience knowledge, the body of which has always been notably fragmentary.”

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