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To understand how the brain works, it’s necessary to map its cellular architecture. This is a challenging problem because of the complex arrangement of nerve cells. A mouse brain has 70 million nerve cells and a human brain about 100 billion. The cells’ axons, which can be as small as 100 nanometers in diameter, travel as far as 500 millimeters through the brain, making tens of thousands of synaptic connections with other nerve cells. While it may still be impractical to map all of these cells and connections, a new imaging approach has greatly improved the speed and resolution at which individual nerve cells can be visualized. This image shows a network of nerve cells in a mouse brain, with the front of the brain on the left.
Fluorescently-labelled mouse brains were chemically treated to make them more transparent. This enables images to be collected from deep within the specimen. The brains were imaged using a high-speed two-photon scanning microscope equipped with a vibratome—a very precise tissue slicer. A large volume of brain tissue was imaged, and subsequently removed using the vibratome. Then the next volume of brain was imaged and removed using the vibratome, and so on, until images of the entire brain were collected.
Once all the images were collected, scientists had to develop methods of working with large amounts of data, including keeping track of each image in relation to its location in the brain. The data allows for 3D computer reconstructions of individual neurons. This data is also made available to other neuroscientists via a website called MouseLight. For a single mouse brain, the scientists collected five million images—a process that took seven to ten days and generated tens of terabytes of data. The brain in the image is about 15 mm from end to end.
Michael Economo, PhD, HHMI Janelia Research Labs, Ashburn, VA