neurons
Celebrating the Power of Connection This Holiday Season
Posted on by Lawrence Tabak, D.D.S., Ph.D.
Happy holidays to one and all! This short science video brings to mind all those twinkling lights now brightening the night, as we mark the beginning of winter and shortest day of the year. This video also helps to remind us about the power of connection this holiday season.
It shows a motor neuron in a mouse’s primary motor cortex. In this portion of the brain, which controls voluntary movement, heavily branched neural projections interconnect, sending and receiving signals to and from distant parts of the body. A single motor neuron can receive thousands of inputs at a time from other branching sensory cells, depicted in the video as an array of blinking lights. It’s only through these connections—through open communication and cooperation—that voluntary movements are possible to navigate and enjoy our world in all its wonder. One neuron, like one person, can’t do it all alone.
This power of connection, captured in this award-winning video from the 2022 Show Us Your Brains Photo and Video contest, comes from Forrest Collman, Allen Institute for Brain Science, Seattle. The contest is part of NIH’s Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative.
In the version above, we’ve taken some liberties with the original video to enhance the twinkling lights from the synaptic connections. But creating the original was quite a task. Collman sifted through reams of data from high-resolution electron microscopy imaging of the motor cortex to masterfully reconstruct this individual motor neuron and its connections.
Those data came from The Machine Intelligence from Cortical Networks (MICrONS) program, supported by the Intelligence Advanced Research Projects Activity (IARPA). It’s part of the Office of the Director of National Intelligence, one of NIH’s governmental collaborators in the BRAIN Initiative.
The MICrONS program aims to better understand the brain’s internal wiring. With this increased knowledge, researchers will develop more sophisticated machine learning algorithms for artificial intelligence applications, which will in turn advance fundamental basic science discoveries and the practice of life-saving medicine. For instance, these applications may help in the future to detect and evaluate a broad range of neural conditions, including those that affect the primary motor cortex.
Pretty cool stuff. So, as you spend this holiday season with friends and family, let this video and its twinkling lights remind you that there’s much more to the season than eating, drinking, and watching football games.
The holidays are very much about the power of connection for people of all faiths, beliefs, and traditions. It’s about taking time out from the everyday to join together to share memories of days gone by as we build new memories and stronger bonds of cooperation for the years to come. With this in mind, happy holidays to one and all.
Links:
“NIH BRAIN Initiative Unveils Detailed Atlas of the Mammalian Primary Motor Cortex,” NIH News Release, October 6, 2021
Forrest Collman (Allen Institute for Brain Science, Seattle)
Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative (NIH)
Show Us Your Brains Photo and Video Contest (BRAIN Initiative)
The Amazing Brain: Where Thoughts Trigger Body Movement
Posted on by Lawrence Tabak, D.D.S., Ph.D.
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:
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: Capturing Neurons in Action
Posted on by Lawrence Tabak, D.D.S., Ph.D.
With today’s powerful imaging tools, neuroscientists can monitor the firing and function of many distinct neurons in our brains, even while we move freely about. They also possess another set of tools to capture remarkable, high-resolution images of the brain’s many thousands of individual neurons, tracing the form of each intricate branch of their tree-like structures.
Most brain imaging approaches don’t capture neural form and function at once. Yet that’s precisely what you’re seeing in this knockout of a movie, another winner in the Show Us Your BRAINs! Photo and Video Contest, supported by NIH’s Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative.
This first-of-its kind look into the mammalian brain produced by Andreas Tolias, Baylor College of Medicine, Houston, and colleagues features about 200 neurons in the visual cortex, which receives and processes visual information. First, you see a colorful, tightly packed network of neurons. Then, those neurons, which were colorized by the researchers in vibrant pinks, reds, blues, and greens, pull apart to reveal their finely detailed patterns and shapes. Throughout the video, you can see neural activity, which appears as flashes of white that resemble lightning bolts.
Making this movie was a multi-step process. First, the Tolias group presented laboratory mice with a series of visual cues, using a functional imaging approach called two-photon calcium imaging to record the electrical activity of individual neurons. While this technique allowed the researchers to pinpoint the precise locations and activity of each individual neuron in the visual cortex, they couldn’t zoom in to see their precise structures.
So, the Baylor team sent the mice to colleagues Nuno da Costa and Clay Reid, Allen Institute for Brain Science, Seattle, who had the needed electron microscopes and technical expertise to zoom in on these structures. Their data allowed collaborator Sebastian Seung’s team, Princeton University, Princeton, NJ, to trace individual neurons in the visual cortex along their circuitous paths. Finally, they used sophisticated machine learning algorithms to carefully align the two imaging datasets and produce this amazing movie.
This research was supported by Intelligence Advanced Research Projects Activity (IARPA), part of the Office of the Director of National Intelligence. The IARPA is one of NIH’s governmental collaborators in the BRAIN Initiative.
Tolias and team already are making use of their imaging data to learn more about the precise ways in which individual neurons and groups of neurons in the mouse visual cortex integrate visual inputs to produce a coherent view of the animals’ surroundings. They’ve also collected an even-larger data set, scaling their approach up to tens of thousands of neurons. Those data are now freely available to other neuroscientists to help advance their work. As researchers make use of these and similar data, this union of neural form and function will surely yield new high-resolution discoveries about the mammalian brain.
Links:
Tolias Lab (Baylor College of Medicine, Houston)
Nuno da Costa (Allen Institute for Brain Science, Seattle)
R. Clay Reid (Allen Institute)
H. Sebastian Seung (Princeton University, Princeton, NJ)
Machine Intelligence from Cortical Networks (MICrONS) Explorer
Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative (NIH)
Show Us Your BRAINs Photo & Video Contest (BRAIN Initiative)
NIH Support: BRAIN Initiative; Common Fund
The Amazing Brain: Seeing Two Memories at Once
Posted on by Lawrence Tabak, D.D.S., Ph.D.
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
Groundbreaking Study Maps Key Brain Circuit
Posted on by Dr. Francis Collins
Biologists have long wondered how neurons from different regions of the brain actually interconnect into integrated neural networks, or circuits. A classic example is a complex master circuit projecting across several regions of the vertebrate brain called the basal ganglia. It’s involved in many fundamental brain processes, such as controlling movement, thought, and emotion.
In a paper published recently in the journal Nature, an NIH-supported team working in mice has created a wiring diagram, or connectivity map, of a key component of this master circuit that controls voluntary movement. This groundbreaking map will guide the way for future studies of the basal ganglia’s direct connections with the thalamus, which is a hub for information going to and from the spinal cord, as well as its links to the motor cortex in the front of the brain, which controls voluntary movements.
This 3D animation drawn from the paper’s findings captures the biological beauty of these intricate connections. It starts out zooming around four of the six horizontal layers of the motor cortex. At about 6 seconds in, the video focuses on nerve cell projections from the thalamus (blue) connecting to cortex nerve cells that provide input to the basal ganglia (green). It also shows connections to the cortex nerve cells that input to the thalamus (red).
At about 25 seconds, the video scans back to provide a quick close-up of the cell bodies (green and red bulges). It then zooms out to show the broader distribution of nerve cells within the cortex layers and the branched fringes of corticothalamic nerve cells (red) at the top edge of the cortex.
The video comes from scientific animator Jim Stanis, University of Southern California Mark and Mary Stevens Neuroimaging and Informatics Institute, Los Angeles. He collaborated with Nick Foster, lead author on the Nature paper and a research scientist in the NIH-supported lab of Hong-Wei Dong at the University of California, Los Angeles.
The two worked together to bring to life hundreds of microscopic images of this circuit, known by the unusually long, hyphenated name: the cortico-basal ganglia-thalamic loop. It consists of a series of subcircuits that feed into a larger signaling loop.
The subcircuits in the loop make it possible to connect thinking with movement, helping the brain learn useful sequences of motor activity. The looped subcircuits also allow the brain to perform very complex tasks such as achieving goals (completing a marathon) and adapting to changing circumstances (running uphill or downhill).
Although scientists had long assumed the cortico-basal ganglia-thalamic loop existed and formed a tight, closed loop, they had no real proof. This new research, funded through NIH’s Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative, provides that proof showing anatomically that the nerve cells physically connect, as highlighted in this video. The research also provides electrical proof through tests that show stimulating individual segments activate the others.
Detailed maps of neural circuits are in high demand. That’s what makes results like these so exciting to see. Researchers can now better navigate this key circuit not only in mice but other vertebrates, including humans. Indeed, the cortico-basal ganglia-thalamic loop may be involved in a number of neurological and neuropsychiatric conditions, including Huntington’s disease, Parkinson’s disease, schizophrenia, and addiction. In the meantime, Stanis, Foster, and colleagues have left us with a very cool video to watch.
Reference:
[1] The mouse cortico-basal ganglia-thalamic network. Foster NN, Barry J, Korobkova L, Garcia L, Gao L, Becerra M, Sherafat Y, Peng B, Li X, Choi JH, Gou L, Zingg B, Azam S, Lo D, Khanjani N, Zhang B, Stanis J, Bowman I, Cotter K, Cao C, Yamashita S, Tugangui A, Li A, Jiang T, Jia X, Feng Z, Aquino S, Mun HS, Zhu M, Santarelli A, Benavidez NL, Song M, Dan G, Fayzullina M, Ustrell S, Boesen T, Johnson DL, Xu H, Bienkowski MS, Yang XW, Gong H, Levine MS, Wickersham I, Luo Q, Hahn JD, Lim BK, Zhang LI, Cepeda C, Hintiryan H, Dong HW. Nature. 2021;598(7879):188-194.
Links:
Brain Basics: Know Your Brain (National Institute of Neurological Disorders and Stroke/NIH)
Dong Lab (University of California, Los Angeles)
Mark and Mary Stevens Neuroimaging and Informatics Institute (University of Southern California, Los Angeles)
The Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative (NIH)
NIH Support: Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Deafness and Other Communication Disorders; National Institute of Mental Health
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