Snapshots of Life: Neurons in a New Light

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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Cool Videos: Flashes of Neuronal Brilliance

When you have a bright idea or suddenly understand something, you might say that a light bulb just went on in your head. But, as the flashing lights of this very cool video show, the brain’s signaling cells, called neurons, continually switch on and off in response to a wide range of factors, simple or sublime.

The technology used to produce this video—a recent winner in the Federation of American Societies for Experimental Biology’s BioArt contest—takes advantage of the fact that whenever a neuron is activated, levels of calcium increase inside the cell. To capture that activity, graduate student Caitlin Vander Weele in Kay M. Tye’s lab at the Picower Institute for Learning and Memory, Massachusetts Institute of Technology (MIT), Cambridge, MA, engineered neurons in a mouse’s brain to produce a bright fluorescent signal whenever calcium increases. Consequently, each time a neuron was activated, the fluorescent indicator lit up and the changes were detected with a miniature microscope. The brighter the flash, the greater the activity!

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Talking Music and Science with Yo-Yo Ma

It’s not every day that an amateur guitar picker gets to play a duet with an internationally renowned classical cellist. But that was my thrill this week as I joined Yo-Yo Ma in a creative interpretation of the traditional song, “How Can I Keep from Singing?” Our short jam session capped off Mr. Ma’s appearance as this year’s J. Edward Rall Cultural Lecture.

The event, which counts The Dalai Lama, Maya Angelou, and Atul Gawande among its distinguished alumni, this year took the form of a conversation on the intersection of music and science—and earned a standing ovation from a packed house of researchers, patients, and staff here on the National Institutes of Health (NIH) campus in Bethesda, MD.

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Summer Reading Suggestions from Scientists: Karl Deisseroth

Summer Reading

Non-Science Selection:

Romila Thapar, History of Early India from Origins to AD 1300. Last January, I was traveling in several cities in India and asked my hosts far too many questions about early Indian history. In the end, one of them (Narasimhan Ram, publisher of the newspaper The Hindu) gave me a number of books, including this text written by a leading Indian historian Romila Thapar. Beyond Thapar’s erudite and level-headed historical scholarship, she did not refrain from fascinating speculation. For example, she speculates on the strongest initial threads of political power, beyond conquest, arising in ritual and culture—much discussed, but here tied to specific archaeological/prehistorical data. Although the specifics in the book itself are on the movement of peoples, conflicts, and cultural shifts that defined the early demographics, politics, and linguistic structures of the Indian subcontinent, the big ideas map readily onto issues that are pressing in the modern world, regarding migration and the sources of cultural authority. The themes of human history that we are reliving today are so vivid, that every few pages a sentence or paragraph would leap out from the page, and I found I had to stop and put down the book for quite some time before continuing—unusual (at least for me) in reading a text of this kind.

Science Selection:

Primo Levi, The Periodic Table. Every few years, rereading this brief masterpiece published by such a gifted writer, chemist, and direct witness to the extremes of the human experience is rewarding in a new way. The vignettes within this volume, at each reading, seem to provide a fresh perspective on the human condition, and remain relevant despite (or perhaps because of) the rapidity of change in this condition. Among its more explicitly scientific themes, the special beauty of chemistry shines forth throughout (with particular resonance for me, as with many biologists, since my own first steps toward science were from a foundation of organic and synthetic chemistry, and still to this day all of my approaches to neuroscience and psychiatry remain rooted in chemistry). The book is also autobiographical and historical, infused with Levi’s personal perspective on the horrific sociology of rising totalitarianism; tragically, this perspective may be increasingly relevant today, and historians, linguists, social scientists, anthropologists, and biologists all find meaning here. The book is composed of many independent short chapters, each titled by an element—and each reader seems to end up with a different list of favorites (the book includes purely fictional components, and, if you only have time for one of the more imaginative chapters to form an opinion of those, you can start with my personal favorite among the historical fantasies, “Lead”).


Karl Deisseroth

Karl Deisseroth
Credit: Alison Yin/ AP Images for HHMI

Karl Deisseroth, MD, PhD is the D.H. Chen Professor of Bioengineering and of Psychiatry and Behavioral Sciences at Stanford University; a foreign adjunct professor at Karolinska Institutet, Stockholm; a Howard Hughes Medical Institute investigator; and a visiting professor at Keio University, Tokyo. Dr. Deisseroth has developed a number of innovative research tools to study the brain, human behavior, and mental illness. Since 2014, Dr. Deisseroth has received two Dickson Prizes, the Albany Prize in Medicine and Biomedical Research, the Lurie Prize in Biomedical Sciences, and the Breakthrough Prize in Life Science.

Creative Minds: Reverse Engineering Vision

Networks of neurons in the mouse retina

Caption: Networks of neurons in the mouse retina. Green cells form a special electrically coupled network; red cells express a distinctive fluorescent marker to distinguish them from other cells; blue cells are tagged with an antibody against an enzyme that makes nitric oxide, important in retinal signaling. Such images help to identify retinal cell types, their signaling molecules, and their patterns of connectivity.
Credit: Jason Jacoby and Gregory Schwartz, Northwestern University

For Gregory Schwartz, working in total darkness has its benefits. Only in the pitch black can Schwartz isolate resting neurons from the eye’s retina and stimulate them with their natural input—light—to get them to fire electrical signals. Such signals not only provide a readout of the intrinsic properties of each neuron, but information that enables the vision researcher to deduce how it functions and forges connections with other neurons.

The retina is the light-sensitive neural tissue that lines the back of the eye. Although only about the size of a postage stamp, each of our retinas contains an estimated 130 million cells and more than 100 distinct cell types. These cells are organized into multiple information-processing layers that work together to absorb light and translate it into electrical signals that stream via the optic nerve to the appropriate visual center in the brain. Like other parts of the eye, the retina can break down, and retinal diseases, including age-related macular degeneration, retinitis pigmentosa, and diabetic retinopathy, continue to be leading causes of vision loss and blindness worldwide.

In his lab at Northwestern University’s Feinberg School of Medicine, Chicago, Schwartz performs basic research that is part of a much larger effort among vision researchers to assemble a parts list that accounts for all of the cell types needed to make a retina. Once Schwartz and others get closer to wrapping up this list, the next step will be to work out the details of the internal wiring of the retina to understand better how it generates visual signals. It’s the kind of information that holds the key for detecting retinal diseases earlier and more precisely, fixing miswired circuits that affect vision, and perhaps even one day creating an improved prosthetic retina.

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