Neuroscientists at 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. The data are being released pre-publication in the spirit of open science initiatives that have become familiar in digital astronomy (e.g., Sloan Digital Sky Survey) but are not yet as widespread in neurobiology.
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.
“We’re executing a grid-based “shotgun” strategy for neuronal tract tracing that we first proposed a few years ago, and which I am pleased to note has gained acceptance elsewhere within the neuroscience community,” says Partha P. Mitra, Ph.D., the Crick-Clay Professor of Biomathematics at CSHL and director of the Mouse Brain Architecture (MBA) Project. After the initial June 1 release, project data will be made public continuously on a monthly basis, Mitra says.
Project addresses a large gap in knowledge
“Our project seeks to address a remarkable gap in our knowledge of the brain,” Mitra explains. “Our knowledge of how the brain is wired remains piecemeal and partial after a century of intense activity. Francis Crick and Ted Jones emphasized this in an article published in Nature nearly 20 years ago.
Yet to understand how the brain works (or fails to work in neurological or neuropsychiatric disease), it is critical that we understand this wiring diagram more fully.
Further, there remain fundamental questions about brain evolution that cannot be addressed without obtaining such wiring diagrams for the brains of different species.”
The MBA Project, which has received critical funding from the Keck Foundation and from the National Institutes of Health, is distinguished by the approach advocated by Mitra and colleagues in a position paper published in 2009. Mitra there proposed mapping vertebrate brains at what he calls the “mesoscopic” scale, a middle-range amenable to light microscopy, providing far more detail than, for instance, MRI-based methods, and yet considerably less detail than is achievable via electron microscopy (EM).
The latter approach, while useful for mapping synaptic connections between individual neurons, is feasible on a whole-brain basis only for very small brains (e.g. that of the fruitfly) or very small portions of the mouse brain.
The pragmatic approach Mitra advocated and which is realized in this first data release, is to image whole mouse brains in a semi-automated, quality-controlled process using light microscopy and injected neural tracers (both viruses and classically used tracer substances). While the basic methodology has been available for some time, systematically applying it to a grid of locations spanning the entire brain, and digitizing and re-assembling the resulting collection of brains, is a new approach made feasible by the rapidly falling costs of computer storage.
A single mouse brain at light-microscope resolution produces about a terabyte (1 trillion bytes, or 1000 GB) of data; thus, generating and storing the data set currently being gathered would have been prohibitively expensive a decade or so ago.