15th April 2014

Mouse brain is mapped for the first time

Researchers have published the first comprehensive, large-scale data set on how the brain of a mammal is wired, providing a groundbreaking new data resource and fresh insights into how the nervous system processes information.

Credit: Allen Institute for Brain Science

While the human brain contains over 100 billion individual neurons, the mouse brain contains 75 million. However, the two structures are very similar, making it possible to compare them and identify many important processes. As computer power continues to advance exponentially, it is becoming possible to model networks of neurons in greater and greater detail. The first complete simulation of a single neuron was perfected in 2005; this was followed by a neocortical column with 10,000 neurons in 2008; then a cortical mesocircuit with 1,000,000 neurons in 2011. Now, a team of researchers from the Allen Institute in Seattle has achieved a major milestone by simulating an entire mouse brain, containing 75 million neurons. If trends continue, entire human brains could be modelled within the next decade.

A landmark study published this month in the journal Nature both describes the publicly available Allen Mouse Brain Connectivity Atlas, and demonstrates the exciting new 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 standardised, 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 – which took four years of work to collect – the researchers were able to demonstrate highly specific patterns in the connections among different brain regions. The strengths of these connections were found to vary with greater than five orders of magnitude, balancing a small number of strong connections with a large number of weak connections.

The researchers set out to create a wiring diagram of the brain – known as a "connectome" – to illustrate short and long-range connections using genetically-engineered viruses, able to trace and illuminate individual neurons. To get a truly comprehensive view, imaging data was collected at resolutions smaller than a micrometre from over 1,700 mouse brains.

"The data for the Allen Mouse Brain Connectivity Atlas was collected in a way that’s never been done before," says Zeng. "Standardising 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 over 1.8 petabytes of data – equivalent to 24 years of continuous HD video. The team behind it has been steadily releasing new data since November 2011; and in March, they released the last major update, though the resource will continue to be updated as technology develops and researchers are able to add more new types of connectivity data.

"The Allen Mouse Brain Connectivity Atlas provides an initial road-map of the brain, at the level of interstate highways and major cities that they link," explains David Anderson, Professor of Biology 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."

With the Nature publication, Allen Institute scientists have already begun to demonstrate the power of analysis contained within the Atlas. By analysing their 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 visualised in 3D.

The Atlas will serve as an invaluable tool for neuroscientists all over the world, long into the future. "Previously, the scientific community had to rely on incomplete, fragmented data sets, like small pieces of a map but at different scales and resolutions, so it was impossible to see the bigger picture," explains Professor Ed Callaway, in the Systems Neurobiology Laboratories at the Salk Institute for Biological Studies. “Now, we have instant access to complete and consistent data across the entire brain, and the suite of web-based analytic and display tools make it easy to find what you need and to see it in 3D.

"Who you are – all your thoughts and actions your entire life – is based on connections between neurons," Callaway continues. "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."

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