Neuroscience  

The new Allen Brain Atlas combines neuroimaging and tissue staining to offer an unprecedented level of resolution. The high-resolution brain map features 862 brain structures from a single donor brain.

Researchers at the Allen Brain Institute, have developed the first whole human brain map at cellular resolution. The dataset combines neuroimaging and comprehensive mapping of brain regions. This digital human brain atlas will allows researchers to investigate the structural basis of human brain function at a resolution never possible before.

The Allen Human Brain Atlas is a unique multi-modal atlas that maps gene expression across the human brain. The model integrates anatomic and genomic information, available data modalities include magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), histology, and gene expression data derived from both microarray and in situ hybridization (ISH) approaches.

"Essentially what we were trying to do is to create a new reference standard for a very fine anatomical structural map of the complete human brain."

Some of the key features include an "all genes, all structures" microarray survey spatially mapped to the MRI, ISH cellular resolution image data for selected genes in specific brain regions, and an annotated human brain atlas guide.

Now with the latest updates to the Human Brain Atlas, users can navigate the brain as easily as using Google Maps. The work was published recently in The Journal of Comparative Neurology.

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“Essentially what we were trying to do is to create a new reference standard for a very fine anatomical structural map of the complete human brain,” says Ed Lein, principal investigator on the project. “It may seem a little bit odd, but actually we are a bit lacking in types of basic reference materials for mapping the human brain that we have in other organisms like mouse or like monkey, and that is in large part because of the enormous size and complexity of the human brain.”

The project, which has already been running for five years, focused on a single healthy postmortem brain from a 34-year-old woman. The research team took a complete scan of the organ, which allowed them to capture both overall brain structure and the connectivity of brain fibers.

The researchers next sliced the brain into 2,716 very thin sections for fine-scale, cellular analysis.

The key step in creating a complete brain atlas was combining broad-scale, high-resolution brain imaging data with detailed cellular-level mapping, which the researchers then annotated with the brain structures they identified. This work is now publically available as the Allen Human Brain Atlas.

"Because of the labor intensiveness of doing this, it always lives in the scale of a single brain,” Lein says, “and you really go to town in trying to understand everything you can about that one individual."

Other researchers argue that the work is too discrete, being from one subject, and that it will be inconclusive to make any broad ranging neuroscience observations from the data.

A different map of the brain was published earlier this year by the Human Connectome Project. The main difference is the Allen study used only one brain, while the Human Connectome Project mapped 210 brains.

In spite of the critics,  the effort marks a marked advance in our understanding of brain anatomy. “There simply hasn't been a complete map of the human brain as a reference piece of material for anyone studying any part of the brain,” Lein says, “and this is a completely essential part of doing research.”

The Allen Human Brain Atlas features anatomic and gene-based search options as well as interactive viewing with the Brain Explorer 3D software.

SOURCE  Scientific American, Allen Brain Institute

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 Neuroscience  

Scientists from the Allen Institute for Brain Science in Seattle have built two new brain maps: one of gene expression in the developing human brain, and another of neural networks in a mouse brain. The maps, which are publicly available, will serve as resources for researchers around the world.

Researchers from the Allen Institute for Brain Science have published the first comprehensive, large-scale data set on how the brain of a mammal is wired, providing a groundbreaking data resource and fresh insights into how the nervous system processes information. Their landmark paper in the journal Nature both describes the publicly available Allen Mouse Brain Connectivity Atlas, and demonstrates the exciting knowledge that can be gleaned from this valuable resource.

“Understanding how the brain is wired is among the most crucial steps to understanding how the brain encodes information,” explains Hongkui Zeng, Senior Director of Research Science at the Allen Institute for Brain Science. “The Allen Mouse Brain Connectivity Atlas is a standardized, quantitative, and comprehensive resource that will stimulate exciting investigations around the entire neuroscience community, and from which we have already gleaned unprecedented details into how structures are connected inside the brain.”

Using the data, Allen Institute scientists were able to demonstrate that there are highly specific patterns in the connections among different brain regions, and that the strengths of these connections vary with greater than five orders of magnitudes, balancing a small number of strong connections with a large number of weak connections. This publication comes just as the research team wraps up more than four years of work to collect and make publicly available the data behind the Allen Mouse Brain Connectivity Atlas project, with the completion of the Atlas announced in March 2014.

"The kind of analysis we have done so far is just the beginning of the deep analysis of the wiring patterns of different brain circuits made possible by this unique collection of data."

The human brain is among the most complex structures in the entire universe, containing roughly 100 billion neurons—as many stars as are in the Milky Way. The mouse brain’s 75 million neurons, arranged in a roughly similar structure to the human brain, provide a powerful model system by which to understand how nerve cells of the human brain connect, process and encode information.

Despite the foundational need to understand how areas of the brain are connected, the only species for which we have a complete wiring diagram is the simple microscopic worm C. elegans—a far simpler system, with only 302 neurons, compared to the human or any other mammalian nervous system.

Scientists at the Allen Institute set out to create a wiring diagram of the brain—also known as a connectome—to illustrate short and long-range connections using genetically-engineered viruses that could trace and illuminate individual neurons. In order to get a truly comprehensive view, scientists collected imaging data at resolutions smaller than a micrometer from more than 1,700 mouse brains, each of which was divided into 140 serial sections. “The data for the Allen Mouse Brain Connectivity Atlas was collected in a way that’s never been done before,” says Zeng. “Standardizing the data generation process allowed us to create a 3D common reference space, meaning we could put the data from all of our thousands of experiments next to each other and compare them all in a highly quantitative way at the same time.”

The Allen Mouse Brain Connectivity Atlas contains more than 1.8 petabytes of data—the equivalent of 23.9 years of continuous HD video—all of which is freely available online to the entire community. The research team behind the Atlas has been steadily releasing new data since November 2011; and in March, they released the last major update to the Atlas, though the resource will continue to be updated as technology develops and researchers are able to add more new types of connectivity data. Like all of the Allen Brain Atlas resources, the data and the tools to browse and analyze them are freely available to the public at www.brain-map.org.

As a freely available resource, the Allen Mouse Brain Connectivity Atlas is an invaluable tool for neuroscientists with questions about the nature of the brain’s connections.

"The Allen Mouse Brain Connectivity Atlas provides an initial road-map of the brain, at the level of interstate highways and the major cities that they link,” explains David Anderson, Professor of Biology and Howard Hughes Medical Institute Investigator at the California Institute of Technology. “Smaller road networks and their intersections with the interstates will be the next step, followed by maps of local streets in different municipalities. This information will provide a framework for what we ultimately want to understand: ‘traffic patterns’ of information flow in the brain during various activities such as decision-making, mapping of the physical environment, learning and remembering, and other cognitive or emotional processes."

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With the Nature publication, Allen Institute scientists have already begun to demonstrate the power of analysis contained within the Atlas. By analyzing the data, Zeng and her team were able to discover several interesting properties of the mouse brain’s connectome. For example, there are extensive connections across the two hemispheres with mirror-image symmetry. Pathways belonging to different functional circuits in the brain can be identified and their relationships and intersections visualized in 3D. Finally, there is a great degree of variation in the strengths of all the connections–ranging beyond five orders of magnitude—and an intriguing balance between a small number of strong connections and a large number of weak connections.

These discoveries illustrate the need for a quantitative understanding and a global view of the brain’s connectivity patterns, since a quantitative approach can describe the relative strength of different connections instead of the simple presence or absence descriptions that are inherent to a more qualitative approach. These more accurate comparisons are uniquely enabled by the Atlas, Zeng says.

“The purpose of the Atlas is to create a new way to map the brain’s vast connections systematically and rapidly, and to develop a platform to present the data to users and help them navigate in the friendliest possible way,” explains Zeng. “But the kind of analysis we have done so far is just the beginning of the deep analysis of the wiring patterns of different brain circuits made possible by this unique collection of data.”

Maintaining the Allen Mouse Brain Connectivity Atlas is a continuous effort. After the completion of the Atlas as originally scoped in March 2014, scientists will continue to update the Atlas with profiles of more individual nerve cell types as they become available. Researchers at the Allen Institute are also poised to dive more deeply into the data they have already collected, and will focus more intently on studying the connections between different types of neurons in the same or neighboring regions – the city roads and local streets that, together with the interstates, form the hierarchical neural networks.

“Who you are—all your thoughts and actions your entire life—is based on connections between neurons,” explains Ed Callaway, Professor in the Systems Neurobiology Laboratories at the Salk Institute for Biological Studies. “So if we want to understand any of these processes or how they go wrong in disease, we have to understand how those circuits function. Without an atlas, we couldn’t hope to gain that understanding.”



SOURCE  Allen Institute for Brain Science

By 33rd Square

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