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HARVARD GAZETTE ARCHIVES

Seeing seeing in action

New uses of imaging techniques broadens world of study

By Alvin Powell
Harvard News Office

Harvard Medical School researchers are seeing what seeing does to the brains of animals and making images that show for the first time single brain cells working together.

Clay Reid
Professor of Neurobiology Clay Reid and colleagues from Harvard Medical School combine existing imaging techniques in newly powerful ways in order to create high-resolution movies of the working brain. (Staff photo Kris Snibbe/Harvard News Office)

The work, by Professor of Neurobiology Clay Reid and colleagues from Harvard Medical School, combines existing imaging techniques to create high-resolution movies of the working brain.

Previous techniques have been able to measure the firing of single brain cells, but have done so blindly. Reid said the old technology is like walking through a cocktail party with one's eyes closed and hearing conversations but never being exactly sure who's speaking. The new techniques take those blinders off, allowing researchers to even make time-lapse images of groups of nerve cells firing in response to visual stimulation.

"The new technology allows us to see it all at a glance," Reid said. "We can look at all 200 neurons [at once]."

The advance opens doors for researchers to understand the brain's functioning at a level of detail not possible before and has potential applications in the understanding of brain diseases, such as Alzheimer's.

Reid said his own work will continue on the visual cortex, a well-studied part of the brain that still holds many secrets.

"We'll see things we haven't thought of," Reid said.

Reid conducted the research together with research fellows Kenichi Ohki and Sooyoung Chung, graduate student Yeang H. Ch'ng, and instructor in neurobiology Prakash Kara. The group combined two techniques in newly powerful ways, thanks to a recent advance by German researchers.

Specifically, Reid and colleagues employed two-photon-microscopy, which uses lasers to take images from deep inside of tissues. They combined that with a dye that glows in relation to a cell's level of calcium. Since calcium levels rise when a nerve cell fires, the dye allows researchers to see active nerve cells grow brighter and then fade.


Video of Clay Reid

Though both techniques have existed for years, the German researchers figured out how to effectively stain multiple nerve cells with the dye, allowing the technique to be applied to regions of the brain rather than single cells.

Using cats and rats, the researchers showed the animals a variety of images, including both still and moving, and horizontal and vertical. From earlier work by Harvard neurobiologists and Nobel laureates David Hubel and Torsten Wiesel, those images are known to be processed by different patches of the brain's visual cortex.

This relationship between location and function is termed "functional architecture." The precision of the borders between regions and their geometry had been difficult to study with conventional techniques, however. The new ability to image the function of individual neurons opens up the study of brain circuits at a finer level: microfunctional architecture.

The resulting images show dramatically different patterns in the visual cortexes of the cat and rat, with blocks of cells lighting up all at once and then fading in the cat and with single cells lighting up, surrounded by dark, inactive cells in the rat.

Reid said it is known that cats have far better eyesight than rats do, but it's impossible to know whether that difference is the cause for the organizational differences in each creature's visual cortex.

alvin_powell@harvard.edu

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