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Live imaging method brings structure to mapping brain function

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Live imaging method brings structure to mapping brain function

Crucially, THG yields an important optical measure called effective attenuation length (EAL), which is a measure of how much the light is absorbed or scattered as it moves through the tissue. In the study, Yildirim and co-authors show that EAL specifically depends on each region’s unique architecture of cells, blood vessels, and myelin. They measured EAL in each of six visual functional regions and showed that the EAL significantly differed among neighboring visual areas, providing a structural signature of sorts for each functional area. Their measurements were so precise, in fact, that they could show how EAL varied within functional regions, being most unique toward the middle and blending closer to the values of neighboring regions out toward the borders.
In other words, by combining the retinotopic mapping with THG three-photon microscopy, Yildirim said, scientists can identify distinct regions by both their function and structure while continuing to work with animals in live experiments. This can produce more accurate and faster results than making observations during behavior and then dissecting tissue in hopes of relocating those same exact positions in preserved brain sections later.
“We would like to combine the strength of retinotopic mapping with three-photon imaging to get more structural information,” Yildirim says. “Otherwise there may be some discrepancies when you do the live imaging of brain activity but then take the tissue out, stain it and try to find the same region.”
Especially as three-photon microscopy gains wider adoption and imaging speeds improve — right now, imaging a millimeter-deep column of cortex takes about 15 minutes, the authors acknowledge — the team expects that its new method could be used not only for studies of the visual system, but also in regions all around the cortex. Moreover, it may help characterize disease states as well as healthy brain structure and function.
“This advance should enable similar studies of structural and functional coupling in other sensory and non-sensory cortical areas in the brains of mice and other animal models,” they wrote. “We believe that the structural and functional correlation in visual areas that we describe for the first time points to crucial developmental mechanisms that set up these areas, thus our work would lead to a better fundamental understanding of brain development, and of disorders such as Alzheimer’s, stroke, and aging.”
In addition to Yildirim and Sur, the paper’s other authors are Ming Hu, Nhat Le, Hiroki Sugihara, and Peter So.
The National Institutes of Health, the National Science Foundation, The JPB Foundation and the Massachusetts Life Sciences Initiative provided funding for the study.

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