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 .
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.
 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.
Dura-Bernal Lab (State University of New York Downstate, Brooklyn)
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
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.
 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.
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)
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
Posted on by Dr. Francis Collins
Can you identify a familiar pattern in this image’s square grid? Yes, it’s the outline of the periodic table! But instead of organizing chemical elements, this periodic table sorts 46 different types of neurons present in the visual cortex of a mouse brain.
Scientists, led by Hongkui Zeng at the Allen Institute for Brain Science, Seattle, constructed this periodic table by assigning colors to their neuronal discoveries based upon their main cell functions . Cells in pinks, violets, reds, and oranges have inhibitory electrical activity, while those in greens and blues have excitatory electrical activity.
For any given cell, the darker colors indicate dendrites, which receive signals from other neurons. The lighter colors indicate axons, which transmit signals. Examples of electrical properties—the number and intensity of their “spikes”—appear along the edges of the table near the bottom.
To create this visually arresting image, Zeng’s NIH-supported team injected dye-containing probes into neurons. The probes are engineered to carry genes that make certain types of neurons glow bright colors under the microscope.
This allowed the researchers to examine a tiny slice of brain tissue and view each colored neuron’s shape, as well as measure its electrical response. They followed up with computational tools to combine these two characteristics and classify cell types based on their shape and electrical activity. Zeng’s team could then sort the cells into clusters using a computer algorithm to avoid potential human bias from visually interpreting the data.
Why compile such a detailed atlas of neuronal subtypes? Although scientists have been surveying cells since the invention of the microscope centuries ago, there is still no consensus on what a “cell type” is. Large, rich datasets like this atlas contain massive amounts of information to characterize individual cells well beyond their appearance under a microscope, helping to explain factors that make cells similar or dissimilar. Those differences may not be apparent to the naked eye.
Just last year, Allen Institute researchers conducted similar work by categorizing nearly 24,000 cells from the brain’s visual and motor cortex into different types based upon their gene activity . The latest research lines up well with the cell subclasses and types categorized in the previous gene-activity work. As a result, the scientists have more evidence that each of the 46 cell types is actually distinct from the others and likely drives a particular function within the visual cortex.
Publicly available resources, like this database of cell types, fuel much more discovery. Scientists all over the world can look at this table (and soon, more atlases from other parts of the brain) to see where a cell type fits into a region of interest and how it might behave in a range of brain conditions.
 Classification of electrophysiological and morphological neuron types in the mouse visual cortex. N Gouwens NW, et al. Neurosci. 2019 Jul;22(7):1182-1195.
 Shared and distinct transcriptomic cell types across neocortical areas. Tasic B, et al. Nature. 2018 Nov;563(7729):72-78.
Brain Basics: The Life and Death of a Neuron (National Institute of Neurological Disorders and Stroke/NIH)
Cell Types: Overview of the Data (Allen Brain Atlas/Allen Institute for Brain Science, Seattle)
Hongkui Zeng (Allen Institute)
NIH Support: National Institute of Mental Health; Eunice Kennedy Shriver National Institute of Child Health & Human Development