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Snapshots of Life

The Amazing Brain: Where Thoughts Trigger Body Movement

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3D column of red neurons (top) and blue neurons (middle)
Credit: Nicolas Antille, SUNY Downstate Health Sciences University, Brooklyn, NY

You’re looking at a section of a mammalian motor cortex (left), the part of the brain where thoughts trigger our body movements. Part of the section is also shown (right) in higher resolution to help you see the intricate details.

These views are incredibly detailed, and they also can’t be produced on a microscope or any current state-of-the-art imaging device. They were created on a supercomputer. Researchers input vast amounts of data covering the activity of the motor cortex to model this highly detailed and scientifically accurate digital simulation.

The vertical section (left) shows a circuit within a column of motor neurons. The neurons run from the top, where the brain meets the skull, downward to the point that the motor cortex connects with other brain areas.

The various colors represent different layers of the motor cortex, and the bright spots show where motor neurons are firing. Notice the thread-like extensions of the motor neurons, some of which double back to connect cells from one layer with others some distance away. All this back and forth makes it appear as though the surface is unraveling.

This unique imaging was part of this year’s Show Us Your Brain Photo and Video contest, supported by NIH’s Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative. Nicolas Antille, an expert in turning scientific data into accurate and compelling visuals, created the images using a scientific model developed in the lab of Salvador Dura-Bernal, SUNY Downstate Health Sciences University, Brooklyn, NY. In the Dura-Bernal lab, scientists develop software and highly detailed computational models of neural circuits to better understand how they give rise to different brain functions and behavior [1].

Antille’s images make the motor neurons look densely packed, but in life the density would be five times as much. Antille has paused the computer simulation at a resolution that he found scientifically and visually interesting. But the true interconnections among neurons, or circuits, inside a real brain—even a small portion of a real brain—are more complex than the most powerful computers today can fully process.

While Antille is invested in revealing brain circuits as close to reality as possible, he also has the mind of an artist. He works with the subtle interaction of light with these cells to show how many individual neurons form this much larger circuit. Here’s more of his artistry at work. Antille wants to invite us all to ponder—even if only for a few moments—the wondrous beauty of the mammalian brain, including this remarkable place where thoughts trigger movements.

Reference:

[1] NetPyNE, a tool for data-driven multiscale modeling of brain circuits. Dura-Bernal S, Suter BA, Gleeson P, Cantarelli M, Quintana A, Rodriguez F, Kedziora DJ, Chadderdon GL, Kerr CC, Neymotin SA, McDougal RA, Hines M, Shepherd GM, Lytton WW. Elife. 2019 Apr 26;8:e44494.

Links:

Nicolas Antille

Dura-Bernal Lab (State University of New York Downstate, Brooklyn)

Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative (NIH)

Show Us Your BRAINs Photo & Video Contest (BRAIN Initiative)

NIH Support: National Institute of Biomedical Imaging and Bioengineering; National Institute of Neurological Disorders and Stroke; BRAIN Initiative


The Amazing Brain: Tight-Knit Connections

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colored tracts create a model of the entire brain
Credit: Sahar Ahmad, Ye Wu, and Pew-Thian Yap, The University of North Carolina, Chapel Hill

You’ve likely seen pictures of a human brain showing its smooth, folded outer layer, known as the cerebral cortex. Maybe you’ve also seen diagrams highlighting some of the brain’s major internal, or subcortical, structures.

These familiar representations, however, overlook the brain’s intricate internal wiring that power our thoughts and actions. This wiring consists of tightly bundled neural projections, called fiber tracts, that connect different parts of the brain into an integrated neural communications network.

The actual patterns of these fiber tracts are represented here and serve as the featured attraction in this award-winning image from the 2022 Show Us Your BRAINs Photo and Video contest. The contest is supported by NIH’s Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative.

Let’s take a closer look. At the center of the brain, you see some of the major subcortical structures: hippocampus (orange), amygdala (pink), putamen (magenta), caudate nucleus (purple), and nucleus accumbens (green). The fiber tracts are presented as colorful, yarn-like projections outside of those subcortical and other brain structures. The various colors, like a wiring diagram, distinguish the different fiber tracts and their specific connections.

This award-winning atlas of brain connectivity comes from Sahar Ahmad, Ye Wu, and Pew-Thian Yap, The University of North Carolina, Chapel Hill. The UNC Chapel Hill team produced this image using a non-invasive technique called diffusion MRI tractography. It’s an emerging approach with many new possibilities for neuroscience and the clinic [1]. Ahmad’s team is putting it to work to map the brain’s many neural connections and how they change across the human lifespan.

In fact, the connectivity atlas you see here isn’t from a single human brain. It’s actually a compilation of images of the brains of multiple 30-year-olds. The researchers are using this brain imaging approach to visualize changes in the brain and its fiber tracts as people grow, develop, and mature from infancy into old age.

Sahar says their comparisons of such images show that early in life, many dynamic changes occur in the brain’s fiber tracts. Once a person reaches young adulthood, the connective wiring tends to stabilize until old age, when fiber tracts begin to break down. These and other similarly precise atlases of the human brain promise to reveal fascinating insights into brain organization and the functional dynamics of its architecture, now and in the future.

Reference:

[1] Diffusion MRI fiber tractography of the brain. Jeurissen B, Descoteaux M, Mori S, Leemans A. NMR Biomed. 2019 Apr;32(4):e3785.

Links:

Brain Basics: Know Your Brain (National Institute of Neurological Disorders and Stroke/NIH)

Sahar Ahmad (The University of North Carolina, Chapel Hill)

Ye Wu (The University of North Carolina, Chapel Hill)

Pew-Thian Yap (The University of North Carolina, Chapel Hill)

Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative (NIH)

Show Us Your BRAINs Photo & Video Contest (BRAIN Initiative)

NIH Support: BRAIN Initiative; National Institute of Mental Health


The Amazing Brain: Seeing Two Memories at Once

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Light microscopy. Green at top and bottom with a middle blue layer showing cells.
Credit: Stephanie Grella, Boston University, MA

The NIH’s Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative is revolutionizing our understanding of the human brain. As described in the initiative’s name, the development of innovative imaging technologies will enable researchers to see the brain in new and increasingly dynamic ways. Each year, the initiative celebrates some standout and especially creative examples of such advances in the “Show Us Your BRAINs! Photo & Video Contest. During most of August, I’ll share some of the most eye-catching developments in our blog series, The Amazing Brain.

In this fascinating image, you’re seeing two stored memories, which scientists call engrams, in the hippocampus region of a mouse’s brain. The engrams show the neural intersection of a good memory (green) and a bad memory (pink). You can also see the nuclei of many neurons (blue), including nearby neurons not involved in the memory formation.

This award-winning image was produced by Stephanie Grella in the lab of NIH-supported neuroscientist Steve Ramirez, Boston University, MA. It’s also not the first time that the blog has featured Grella’s technical artistry. Grella, who will soon launch her own lab at Loyola University, Chicago, previously captured what a single memory looks like.

To capture two memories at once, Grella relied on a technology known as optogenetics. This powerful method allows researchers to genetically engineer neurons and selectively activate them in laboratory mice using blue light. In this case, Grella used a harmless virus to label neurons involved in recording a positive experience with a light-sensitive molecule, known as an opsin. Another molecular label was used to make those same cells appear green when activated.

After any new memory is formed, there’s a period of up to about 24 hours during which the memory is malleable. Then, the memory tends to stabilize. But with each retrieval, the memory can be modified as it restabilizes, a process known as memory reconsolidation.

Grella and team decided to try to use memory reconsolidation to their advantage to neutralize an existing fear. To do this, they placed their mice in an environment that had previously startled them. When a mouse was retrieving a fearful memory (pink), the researchers activated with light associated with the positive memory (green), which for these particular mice consisted of positive interactions with other mice. The aim was to override or disrupt the fearful memory.

As shown by the green all throughout the image, the experiment worked. While the mice still showed some traces of the fearful memory (pink), Grella explained that the specific cells that were the focus of her study shifted to the positive memory (green).

What’s perhaps even more telling is that the evidence suggests the mice didn’t just trade one memory for another. Rather, it appears that activating a positive memory actually suppressed or neutralized the animal’s fearful memory. The hope is that this approach might one day inspire methods to help people overcome negative and unwanted memories, such as those that play a role in post-traumatic stress disorder (PTSD) and other mental health issues.

Links:

Stephanie Grella (Boston University, MA)

Ramirez Group (Boston University)

Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative (NIH)

Show Us Your BRAINs Photo & Video Contest (BRAIN Initiative)

NIH Support: BRAIN Initiative; Common Fund


Capturing the Extracellular Matrix in 3D Color

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Credit: Sarah Lipp, Purdue University, and Sarah Calve, University of Colorado, Boulder

For experienced and aspiring shutterbugs alike, sometimes the best photo in the bunch turns out to be a practice shot. That’s also occasionally true in the lab when imaging cells and tissues, and it’s the story behind this spectacular image showing the interface of skin and muscle during mammalian development.

Here you see an area of the mouse forelimb located near a bone called the humerus. This particular sample was labeled for laminin, a protein found in the extracellular matrix (ECM) that undergirds cells and tissues to give them mechanical and biochemical support. Computer algorithms were used to convert the original 2D confocal scan into a 3D image, and colorization was added to bring the different layers of tissue into sharper relief.

Skin tissue (bright red and yellow) is located near the top of the image; blood vessels (paler red, orange, and yellow) are in the middle and branching downward; and muscle (green, blue, and purple) makes up the bottom layer.

The image was created by Sarah Lipp, a graduate student in the NIH-supported tissue engineering lab of Sarah Calve. The team focuses on tissue interfaces to better understand the ECM and help devise strategies to engineer musculoskeletal tissues, such as tendon and cartilage.

In February 2020, Lipp was playing around with some new software tools for tissue imaging. Before zeroing in on her main target—the mouse’s myotendinous junction, where muscle transfers its force to tendon, Lipp snapped this practice shot of skin meeting muscle. After processing the practice shot with a color-projecting macro in an image processing tool called Fiji, she immediately liked what she saw.

So, Lipp tweaked the color a bit more and entered the image in the 2020 BioArt Scientific Image & Video Competition, sponsored by the Federation of American Societies for Experimental Biology, Bethesda, MD. Last December, the grad student received the good news that her practice shot had snagged one of the prestigious contest’s top awards.

But she’s not stopping there. Lipp is continuing to pursue her research interests at the University of Colorado, Boulder, where the Calve lab recently moved from Purdue University, West Lafayette, IN. Here’s wishing her a career filled with more great images—and great science!

Links:

Muscle and Bone Diseases (National Institute of Arthritis and Musculoskeletal and Skin Diseases/NIH)

Musculoskeletal Extracellular Matrix Laboratory (University of Colorado, Boulder)

BioArt Scientific Image & Video Competition (Federation of American Societies for Experimental Biology, Bethesda, MD)

NIH Support: National Institute of Arthritis and Musculoskeletal and Skin Diseases


The Hidden Beauty of Intestinal Villi

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Credit: Amy Engevik, Medical University of South Carolina, Charleston.

The human small intestine, though modest in diameter and folded compactly to fit into the abdomen, is anything but small. It measures on average about 20 feet from end to end and plays a big role in the gastrointestinal tract, breaking down food and drink from the stomach to absorb the water and nutrients.

Also anything but small is the total surface area of the organ’s inner lining, where millions of U-shaped folds in the mucosal tissue triple the available space to absorb the water and nutrients that keep our bodies nourished. If these folds, packed with finger-like absorptive cells called villi, were flattened out, they would be the size of a tennis court!

That’s what makes this this microscopic image so interesting. It shows in cross section the symmetrical pattern of the villi (its cells outlined by yellow) that pack these folds. Each cell’s nucleus contains DNA (teal), and the villi themselves are fringed by thousands of tiny bristles, called microvilli (magenta), which are too small to see individually here. Collectively, microvilli make up an absorptive surface, called the brush border, where digested nutrients in the fluid passing through the intestine can enter cells via transport channels.

Amy Engevik, a researcher at the Medical University of South Carolina, Charleston, took this snapshot to show what a healthy intestinal cellular landscape looks like in a young mouse. The Engevik lab studies the dynamic movement of ions, water, and proteins in the intestine—a process that goes wrong in humans born with a rare disorder called microvillus inclusion disease (MVID).

MVID causes chronic gastrointestinal problems in newborn babies, due to defects in a protein that transports various cellular components. Because they cannot properly absorb nutrition from food, these tiny patients require intravenous feeding almost immediately, which carries a high risk for sepsis and intestinal injury.

Engevik and her team study this disease using a mouse model that replicates many of the characteristics of the disorder in humans [1]. Interestingly, when Engevik gets together with her family, she isn’t the only one talking about MVID and villi. Her two sisters, Mindy and Kristen, also study the basic science of gastrointestinal disorders! Instead of sibling rivalry, though, this close alliance has strengthened the quality of her research, says Amy, who is the middle child.

Beyond advancing science and nurturing sisterhood in science, Engevik’s work also captured the fancy of the judges for the Federation of American Societies for Experimental Biology’s annual BioArt Scientific Image and Video Competition. Her image was one of 10 winners announced in December 2020.

Because multiple models are useful for understanding fundamentals of diseases like MVID, Engevik has also developed a large-animal model (pig) that has many features of the human disease [2]. She hopes that her efforts will help to improve our understanding of MVID and other digestive diseases, as well as lead to new, potentially life-saving treatments for babies suffering from MVID.

References:

[1] Loss of MYO5B Leads to reductions in Na+ absorption with maintenance of CFTR-dependent Cl- secretion in enterocytes. Engevik AC, Kaji I, Engevik MA, Meyer AR, Weis VG, Goldstein A, Hess MW, Müller T, Koepsell H, Dudeja PK, Tyska M, Huber LA, Shub MD, Ameen N, Goldenring JR. Gastroenterology. 2018 Dec;155(6):1883-1897.e10.

[2] Editing myosin VB gene to create porcine model of microvillus inclusion disease, with microvillus-lined inclusions and alterations in sodium transporters. Engevik AC, Coutts AW, Kaji I, Rodriguez P, Ongaratto F, Saqui-Salces M, Medida RL, Meyer AR, Kolobova E, Engevik MA, Williams JA, Shub MD, Carlson DF, Melkamu T, Goldenring JR. Gastroenterology. 2020 Jun;158(8):2236-2249.e9.

Links:

Microvillus inclusion disease (Genetic and Rare Diseases Center/NIH)

Digestive Diseases (National Institute of Diabetes and Digestive and Kidney Diseases/NIH)

Amy Engevik (Medical University of South Carolina, Charleston)

Podcast: A Tale of Three Sisters featuring Drs. Mindy, Amy, and Kristen Engevik (The Immunology Podcast, April 29, 2021)

BioArt Scientific Image and Video Competition (Federation of American Societies for Experimental Biology, Bethesda, MD)

NIH Support: National Institute of Diabetes and Digestive and Kidney Diseases


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