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Show Us Your Brain

The Amazing Brain: Shining a Spotlight on Individual Neurons

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A major aim of the NIH-led Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative is to develop new technologies that allow us to look at the brain in many different ways on many different scales. So, I’m especially pleased to highlight this winner of the initiative’s recent “Show Us Your Brain!” contest.

Here you get a close-up look at pyramidal neurons located in the hippocampus, a region of the mammalian brain involved in memory. While this tiny sample of mouse brain is densely packed with many pyramidal neurons, researchers used new ExLLSM technology to zero in on just three. This super-resolution, 3D view reveals the intricacies of each cell’s structure and branching patterns.

The group that created this award-winning visual includes the labs of X. William Yang at the University of California, Los Angeles, and Kwanghun Chung at the Massachusetts Institute of Technology, Cambridge. Chung’s team also produced another quite different “Show Us Your Brain!” winner, a colorful video featuring hundreds of neural cells and connections in a part of the brain essential to movement.

Pyramidal neurons in the hippocampus come in many different varieties. Some important differences in their functional roles may be related to differences in their physical shapes, in ways that aren’t yet well understood. So, BRAIN-supported researchers are now applying a variety of new tools and approaches in a more detailed effort to identify and characterize these neurons and their subtypes.

The video featured here took advantage of Chung’s new method for preserving brain tissue samples [1]. Another secret to its powerful imagery was a novel suite of mouse models developed in the Yang lab. With some sophisticated genetics, these models make it possible to label, at random, just 1 to 5 percent of a given neuronal cell type, illuminating their full morphology in the brain [2]. The result was this unprecedented view of three pyramidal neurons in exquisite 3D detail.

Ultimately, the goal of these and other BRAIN Initiative researchers is to produce a dynamic picture of the brain that, for the first time, shows how individual cells and complex neural circuits interact in both time and space. I look forward to their continued progress, which promises to revolutionize our understanding of how the human brain functions in both health and disease.

References:

[1] Protection of tissue physicochemical properties using polyfunctional crosslinkers. Park YG, Sohn CH, Chen R, McCue M, Yun DH, Drummond GT, Ku T, Evans NB, Oak HC, Trieu W, Choi H, Jin X, Lilascharoen V, Wang J, Truttmann MC, Qi HW, Ploegh HL, Golub TR, Chen SC, Frosch MP, Kulik HJ, Lim BK, Chung K. Nat Biotechnol. 2018 Dec 17.

[2] Genetically-directed Sparse Neuronal Labeling in BAC Transgenic Mice through Mononucleotide Repeat Frameshift. Lu XH, Yang XW. Sci Rep. 2017 Mar 8;7:43915.

Links:

Chung Lab (Massachusetts Institute of Technology, Cambridge)

Yang Lab (University of California, Los Angeles)

Show Us Your Brain! (BRAIN Initiative/NIH)

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

NIH Support: National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; National Institute of Biomedical Imaging and Bioengineering


The Amazing Brain: Zooming Through the Globus Pallidus Externa

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The Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative continues to find new ways to visualize neurons interconnecting into the billions of circuits that control our thoughts, feelings, and movements. This video, another winner in the initiative’s “Show Us Your Brain!” contest, offers a beautiful example of how these imaging techniques are getting better all the time.

The video features a millimeter-thick block of fixed tissue from a part of the mouse brain that’s known for its role in controlling voluntary movement. It’s called the globus pallidus externa (GPE). The video takes us inside the 3D landscape of the GPE, zooming in on the many neural cell bodies (yellow) and their arm-like extensions (red) that receive or transmit information. There’s also another class of neural cells called interneurons (blue) that act only within the circuit.

The video comes from the lab of Kwanghun Chung, Massachusetts Institute of Technology, Cambridge, in collaboration with Byungkook Lim’s group at the University of California, San Diego, and showcases a technique called SHIELD [1]. Brain tissue is extremely delicate to work with and prone to damage. SHIELD, developed in the Chung lab, offers a new way around this longstanding problem.

SHIELD uses polyepoxides, which are epoxy resins often used to produce glues. The researchers’ polyepoxide of choice has a flexible backbone and five branches, which bind to proteins and other molecules in place, including DNA and RNA. The molecule’s flexibility allows it to bind in multiple places along a single biomolecule and form supportive cross-links with other nearby molecules.

All of this support renders the tissue and its biological information extremely stable, even when exposed to heat and other harsh conditions. This makes it possible for researchers to label proteins, RNA, and various other biomolecules of interest simultaneously, as you see shown here in this remarkable video. SHIELD even allowed them to trace the many projections of multiple neural cell types and their connections within the GPE at once.

In the future, the team hopes to learn whether differences in the projection patterns of these neurons or in their molecular details may influence Parkinson’s disease and other illnesses that affect motor control. With this imaging advance and others through the BRAIN Initiative, mapping the biocircuitry of the brain just keeps getting better all the time.

Reference:

[1] Protection of tissue physicochemical properties using polyfunctional crosslinkers. Park YG, Sohn CH, Chen R, McCue M, Yun DH, Drummond GT, Ku T, Evans NB, Oak HC, Trieu W, Choi H, Jin X, Lilascharoen V, Wang J, Truttmann MC, Qi HW, Ploegh HL, Golub TR, Chen SC, Frosch MP, Kulik HJ, Lim BK, Chung K. Nat Biotechnol. 2018 Dec 17.

Links:

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

Chung Lab (Massachusetts Institute of Technology, Cambridge)

Show Us Your Brain! (BRAIN Initiative/NIH)

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

NIH Support: National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; National Institute of Biomedical Imaging and Bioengineering


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