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Brain Cell Analysis

Caption: While analyzing brain cells, a computer program “thinks” about which cellular structure to identify.
Credit: Steven Finkbeiner, University of California, San Francisco and the Gladstone Institutes

For centuries, scientists have trained themselves to look through microscopes and carefully study their structural and molecular features. But those long hours bent over a microscope poring over microscopic images could be less necessary in the years ahead. The job of analyzing cellular features could one day belong to specially trained computers.

In a new study published in the journal Cell, researchers trained computers by feeding them paired sets of fluorescently labeled and unlabeled images of brain tissue millions of times in a row [1]. This allowed the computers to discern patterns in the images, form rules, and apply them to viewing future images. Using this so-called deep learning approach, the researchers demonstrated that the computers not only learned to recognize individual cells, they also developed an almost superhuman ability to identify the cell type and whether a cell was alive or dead. Even more remarkable, the trained computers made all those calls without any need for harsh chemical labels, including fluorescent dyes or stains, which researchers normally require to study cells. In other words, the computers learned to “see” the invisible!


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Steve Ramirez

Steve Ramirez/Joshua Sariñana

Whether it’s lacing up for a morning run, eating blueberry scones, or cheering on the New England Patriots, Steve Ramirez loves life and just about everything in it. As an undergraduate at Boston University, this joie de vivre actually made Ramirez anxious about choosing just one major. A serendipitous conversation helped him realize that all of the amazing man-made stuff in our world has a common source: the human brain.

So, Ramirez decided to pursue neuroscience and began exploring the nature of memory. Employing optogenetics (using light to control brain cells) in mice, he tagged specific neurons that housed fear-inducing memories, making the neurons light sensitive and amenable to being switched on at will.

In groundbreaking studies that earned him a spot in Forbes 2015 “30 Under 30” list, Ramirez showed that it’s possible to reactivate memories experimentally in a new context, recasting them in either a more negative or positive behavior-changing light [1–3]. Now, with support from a 2016 NIH Director’s Early Independence Award, Ramirez, who runs his own lab at Boston University, will explore whether activating good memories holds promise for alleviating chronic stress and psychiatric disease.


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Credit: Raunak Basu, University of Utah, Salt Lake City

The final frontier? Trekkies would probably say it’s space, but mapping the brain—the most complicated biological structure in the known universe—is turning out to be an amazing adventure in its own right. Not only are researchers getting better at charting the brain’s densely packed and varied cellular topography, they are starting to identify the molecules that neurons use to connect into the distinct information-processing circuits that allow all walks of life to think and experience the world.

This image shows distinct neural connections in a cross section of a mouse’s hippocampus, a region of the brain involved in the memory of facts and events. The large, crescent-shaped area in green is hippocampal zone CA1. Its highly specialized neurons, called place cells, serve as the brain’s GPS system to track location. It appears green because these neurons express cadherin-10. This protein serves as a kind of molecular glue that likely imparts specific functional properties to this region. [1]


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Kafui Dzirasa at UMBC

Caption: Kafui Dzirasa (front center) with the current group of Meyerhoff Scholars at University of Maryland, Baltimore County.
Credit: Olubukola Abiona

Kafui Dzirasa keeps an open-door policy in his busy NIH-supported lab at Duke University, Durham, NC. If his trainees have a quick question or just need to discuss an upcoming experiment, they’re always welcome to pull up a chair. The donuts are on him.

But when trainees pop by his office and see he’s out for the day, they have a good idea of what it means. Dzirasa has most likely traveled up to his native Maryland to volunteer as a mentor for students in a college program that will be forever near and dear to him. It’s the Meyerhoff Scholars Program at the University of Maryland, Baltimore County (UMBC). Since its launch in 1988, this groundbreaking program has served as a needed pipeline to help increase diversity in the sciences—with more than 1,000 alumni, including Dzirasa, and 270 current students of all races.


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Mouse Midbrain

Credit: Michael Shribak, Marine Biological Laboratory, Woods Hole, MA

Birds do it, bees do it, and even educated fleas do it. No, not fall in love, as the late Ella Fitzgerald so famously sang. Birds and insects can see polarized light—that is, light waves transmitted in a single directional plane—in ways that provides them with a far more colorful and detailed view of the world than is possible with the human eye.

Still, thanks to innovations in microscope technology, scientists have been able to tap into the power of polarized light vision to explore the inner workings of many complex biological systems, including the brain. In this image, researchers used a recently developed polarized light microscope to trace the spatial orientation of neurons in a thin section of the mouse midbrain. Neurons that stretch horizontally appear green, while those oriented at a 45-degree angle are pinkish-red and those at 225 degrees are purplish-blue. What’s amazing is that these colors don’t involve staining or tagging the cells with fluorescent markers: the colors are generated strictly from the light interacting with the physical orientation of each neuron.


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