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Brain Cell Analysis

Caption: While analyzing brain cells, a computer program “thinks” about which cellular structure to identify.
Credit: Steven Finkbeiner, University of California, San Francisco and the Gladstone Institutes

For centuries, scientists have trained themselves to look through microscopes and carefully study their structural and molecular features. But those long hours bent over a microscope poring over microscopic images could be less necessary in the years ahead. The job of analyzing cellular features could one day belong to specially trained computers.

In a new study published in the journal Cell, researchers trained computers by feeding them paired sets of fluorescently labeled and unlabeled images of brain tissue millions of times in a row [1]. This allowed the computers to discern patterns in the images, form rules, and apply them to viewing future images. Using this so-called deep learning approach, the researchers demonstrated that the computers not only learned to recognize individual cells, they also developed an almost superhuman ability to identify the cell type and whether a cell was alive or dead. Even more remarkable, the trained computers made all those calls without any need for harsh chemical labels, including fluorescent dyes or stains, which researchers normally require to study cells. In other words, the computers learned to “see” the invisible!

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Mammalian hippocampal tissue

Caption: Mammalian hippocampal tissue. Immunofluorescence microscopy showing neurons (blue) interacting with neural astrocytes (red) and oligodendrocytes (green).
Credit: Jonathan Cohen, Fields Lab, National Institute of Neurological Disorders and Stroke, NIH

There’s been considerable debate about whether the human brain has the capacity to make new neurons into adulthood. Now, a recently published study offers some compelling new evidence that’s the case. In fact, the latest findings suggest that a healthy person in his or her seventies may have about as many young neurons in a portion of the brain essential for learning and memory as a teenager does.

As reported in the journal Cell Stem Cell, researchers examined the brains of healthy people, aged 14 to 79, and found similar numbers of young neurons throughout adulthood [1]. Those young neurons persisted in older brains that showed other signs of decline, including a reduced ability to produce new blood vessels and form new neural connections. The researchers also found a smaller reserve of quiescent, or inactive, neural stem cells in a brain area known to support cognitive-emotional resilience, the ability to cope with and bounce back from stressful circumstances.

While more study is clearly needed, the findings suggest healthy elderly people may have more cognitive reserve than is commonly believed. However, the findings may also help to explain why even perfectly healthy older people often find it difficult to face new challenges, such as travel or even shopping at a different grocery store, that wouldn’t have fazed them earlier in life.

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Credit: Wellcome Centre for Human Neuroimaging, University College London.

In recent years, researchers fueled by the BRAIN Initiative and many other NIH-supported efforts have made remarkable progress in mapping the human brain in all its amazing complexity. Now, a powerful new imaging technology promises to further transform our understanding [1]. This wearable scanner, for the first time, enables researchers to track neural activity in people in real-time as they do ordinary things—be it drinking tea, typing on a keyboard, talking to a friend, or even playing paddle ball.

This new so-called magnetoencephalography (MEG) brain scanner, which looks like a futuristic cross between a helmet and a hockey mask, is equipped with specialized “quantum” sensors. When placed directly on the scalp surface, these new MEG scanners can detect weak magnetic fields generated by electrical activity in the brain. While current brain scanners weigh in at nearly 1,000 pounds and require people to come to a special facility and remain absolutely still, the new system weighs less than 2 pounds and is capable of generating 3D images even when a person is making motions.

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MEMOIR cells

Caption: MEMOIR cells variably activate (cyan). The recorded information is then read out to visualize certain RNA transcripts (red).
Credit: Elowitz and Cai Labs, Caltech, Pasadena, CA

One of the most fascinating challenges in biology is understanding how a single cell divides and differentiates to form a complex, multicellular organism. Scientists can learn a lot about this process by tracking time-lapse images through a microscope. But gazing through a lens has its limitations, especially in the brain and other opaque and inaccessible tissues and organs.

With support from a 2017 NIH Director’s Transformative Research Program, a California Institute of Technology (Caltech) team now has a way around this problem. Rather than watching or digging information out of cells, the team has learned how to program cells to write their own molecular memoirs. These cells store the information right in their own genomic hard drives. Even better, that information is barcoded, allowing researchers to read it out of the cells without dissecting tissue. The programming can be performed in many different cell types, including stem or adult cells in tissues throughout the body.

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Zebrafish brain

Credit: Marina Venero Galanternik, Daniel Castranova, Tuyet Nguyen, and Brant M. Weinstein, NICHD, NIH

There are trash bins in our homes, on our streets, and even as a popular icon on our desktop computers. And as this colorful image shows, trash bins of the cellular variety are also important in the brain.

This image—a winner in the Federation of American Societies for Experimental Biology’s 2017 BioArt competition—shows the brain of an adult zebrafish, a popular organism for studying how the brain works. It captures dense networks of blood vessels (red) lining the outer surface of the brain. Next to many of these vessels sit previously little-studied cells called fluorescent granular perithelial cells (yellowish green). Researchers now believe these cells, often shortened to FGPs, act much like trash receptacles that continuously take in and store waste products to keep the brain tidy and functioning well.

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