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Mapping the Brain’s Memory Bank

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There’s a lot of groundbreaking research now underway to map the organization and internal wiring of the brain’s hippocampus, essential for memory, emotion, and spatial processing. This colorful video depicting a mouse hippocampus offers a perfect case in point.

The video presents the most detailed 3D atlas of the hippocampus ever produced, highlighting its five previously defined zones: dentate gyrus, CA1, CA2, CA3, and subiculum. The various colors within those zones represent areas with newly discovered and distinctive patterns of gene expression, revealing previously hidden layers of structural organization.

For instance, the subiculum, which sends messages from the hippocampus to other parts of the brain, includes several subregions. The subregions include the three marked in red, yellow, and blue at about 23 seconds into the video.

How’d the researchers do it? In the new study, published in Nature Neuroscience, the researchers started with the Allen Mouse Brain Atlas, a rich, publicly accessible 3D atlas of gene expression in the mouse brain. The team, led by Hong-Wei Dong, University of Southern California, Los Angeles, drilled down into the data to pull up 258 genes that are differentially expressed in the hippocampus and might be helpful for mapping purposes.

Some of those 258 genes were generally expressed only in previously defined portions of the hippocampus. Others were “turned on” only in discrete portions of known hippocampal domains, leading the researchers to define 20 distinct subregions that hadn’t been recognized before.

Combining these data, sophisticated analytical tools, and plenty of hard work, the team assembled this detailed atlas, together with connectivity data, to create a detailed wiring diagram. It includes about 200 signaling pathways that show how all those subregions network together and with other portions of the brain.

What’s really interesting is that the data also showed that these components of the hippocampus contribute to three relatively independent brain-wide communication networks. While much more study is needed, those three networks appear to relate to distinct functions of the hippocampus, including spatial navigation, social behaviors, and metabolism.

This more-detailed view of the hippocampus is just the latest from the NIH-funded Mouse Connectome Project. The ongoing project aims to create a complete connectivity atlas for the entire mouse brain.

The Mouse Connectome Project isn’t just for those with an interest in mice. Indeed, because the mouse and human brain are similarly organized, studies in the smaller mouse brain can help to provide a template for making sense of the larger and more complex human brain, with its tens of billions of interconnected neurons.

Ultimately, the hope is that this understanding of healthy brain connections will provide clues for better treating the brain’s abnormal connections and/or disconnections. They are involved in numerous neurological conditions, including Alzheimer’s disease, Parkinson’s disease, and autism spectrum disorder.

Reference:

[1] Integration of gene expression and brain-wide connectivity reveals the multiscale organization of mouse hippocampal networks. Bienkowski MS, Bowman I, Song MY, Gou L, Ard T, Cotter K, Zhu M, Benavidez NL, Yamashita S, Abu-Jaber J, Azam S, Lo D, Foster NN, Hintiryan H, Dong HW. Nat Neurosci. 2018 Nov;21(11):1628-1643.

Links:
Mouse Connectome Project (University of Southern California, Los Angeles)

Human Connectome Project (USC)

Allen Brain Map (Allen Institute, Seattle)

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

NIH Support: National Institute of Mental Health; National Cancer Institute


Halloween Fly-Through of a Mouse Skull

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Credit: Chai Lab, University of Southern California, Los Angeles

Halloween is full of all kinds of “skulls”—from spooky costumes to ghoulish goodies. So, in keeping with the spirit of the season, I’d like to share this eerily informative video that takes you deep inside the real thing.


Fighting Cancer with Natural Killer Cells

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GIF of immune cells attacking

Credit: Michele Ardolino, University of Ottawa, and Brian Weist, Gilead Sciences, Foster City, CA

Cancer immunotherapies, which enlist a patient’s own immune system to attack and shrink developing tumors, have come a long way in recent years, leading in some instances to dramatic cures of widely disseminated cancers. But, as this video highlights, new insights from immunology are still being revealed that may provide even greater therapeutic potential.

Our immune system comes equipped with all kinds of specialized cells, including the infection-controlling Natural Killer (NK) cells. The video shows an army of NK cells (green) attacking a tumor in a mouse (blood vessels, blue) treated with a well-established type of cancer immunotherapy known as a checkpoint inhibitor. What makes the video so interesting is that researchers didn’t think checkpoint inhibitors could activate NK cells.


Putting Bone Metastasis in the Spotlight

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When cancers spread, or metastasize, from one part of the body to another, bone is a frequent and potentially devastating destination. Now, as you can see in this video, an NIH-funded research team has developed a new system that hopefully will provide us with a better understanding of what goes on when cancer cells invade bone.

In this 3D cross-section, you see the nuclei (green) and cytoplasm (red) of human prostate cancer cells growing inside a bioengineered construct of mouse bone (blue-green) that’s been placed in a mouse. The new system features an imaging window positioned next to the new bone, which enabled the researchers to produce the first series of direct, real-time micrographs of cancer cells eroding the interior of bone.


3D Action Film Stars Cancer Cell as the Villain

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For centuries, microscopes have brought to light the otherwise invisible world of the cell. But microscopes don’t typically visualize the dynamic world of the cell within a living system.

For various technical reasons, researchers have typically had to displace cells, fix them in position, mount them onto slides, and look through a microscope’s viewfinder to see the cells. It can be a little like trying to study life in the ocean by observing a fish cooped up in an 8-gallon tank.

Now, a team partially funded by NIH has developed a new hybrid imaging technology to produce amazing, live-action 3D movies of living cells in their more natural state. In this video, you’re looking at a human breast cancer cell (green) making its way through a blood vessel (purple) of a young zebrafish.

At first, the cancer cell rolls along rather freely. As the cell adheres more tightly to the blood vessel wall, that rolling motion slows to a crawl. Ultimately, the cancer cell finds a place to begin making its way across and through the blood vessel wall, where it can invade other tissues.


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