PSC Scientists Co-Author Paper on Wiring Diagram of the Brain

Nature – March 10 Issue Cover

Wetzel and Hood collaborated with a team at Harvard University led by Clay Reid, professor of neurobiology at the Harvard Medical School and Center for Brain Science. The Harvard-PSC team exploited improvements in computer speed and storage capacity available at PSC that made it possible to transmit and process more than three-million high-resolution images from a pinpoint-sized region of a mouse brain. Starting with these very thin-slice (40 nanometers) images — obtained at Harvard via electron microscopy (EM), Wetzel and Hood stitched together a large-scale single-section mosaic. From these sections, they then reconstructed a 3D volume (encompassing millions of cubic micrometres) which made it possible for the Harvard team to painstakingly trace interconnections among selected neurons, in effect mapping a wiring diagram of a portion of the mouse visual cortex.

To get an idea of the amount of cortical information captured in each section, Reid analogizes to slicing a wedge of cheese. If each slice were a millimeter thick like a thin slice of cheese (instead of 40 nanometers), and the lateral dimensions increased by the same proportion, each slice would cover an area bigger than an NBA basketball court.

Hood and Wetzel used various software methods — fast Fourier transform correlations and other search methods — to find features in overlapping camera frames for alignment into a single mosaic. This process matches adjacent frames both spatially and in intensity to produce a nearly seamless image (about 10 gigapixels) of each section. They then apply a non-linear registration algorithm to map each section to its neighboring sections, compensating for deformations that inevitably occur when cutting tissue so thinly. Finally, a multiscale 3-D alignment stacks these local maps to construct a finished volume (10 teravoxels) for viewing and analysis.

By tracing interconnections within this volume, the Harvard researchers produced new insights into how the brain functions, finding that neurons tasked with suppressing brain activity seem to be randomly wired, putting the lid on local groups of neurons all at once rather than picking and choosing. Such findings are important because many neurological conditions, such as epilepsy, are the result of neural inhibition gone awry.

“This is just the iceberg’s tip,” said Reid. “Within ten years I’m convinced we’ll be imaging the activity of thousands of neurons in a living brain. In a visual circuit, we’ll interpret the data to reconstruct what an animal actually sees. By that time, with the anatomical imaging, we’ll also know how it’s all wired together.”

For now, Reid and his colleagues are working to scale up this platform to generate larger data sets. “How the brain works is one of the greatest mysteries in nature,” Reid added, “and this research presents a new and powerful way for us to explore that mystery.”

Article and video about this research from Focus, Harvard Medical School research magazine: http://www.focushms.com/features/web-crawling-the-brain/