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Carmen S. Dence collaborates with numerous researchers Picturing Our Past
				Glowing colors Illuminated jellyfish genes transform brain research By Darrell E. Ward University researchers are transplanting jellyfish genes into mice to watch how neural connections change in the brains of living animals. The development represents the merging of several technologies and enables researchers to watch changes inside living animals during normal development and during disease progression in a relatively noninvasive way. Photo by Bob Boston Jeff W. Lichtman, M.D., Ph.D., sees neurons in a new light. Here, a two-photon microscope -- which features a powerful infrared laser that selectively stimulates the fluorescent proteins in nerve cells deep within the brain to glow -- illuminates his face. "This work represents a new approach to studying the biology of whole, living animals," said Jeff W. Lichtman, M.D., Ph.D., professor of anatomy and neurobiology. "I believe these methods will transform not only neurobiology, but also immunology and studies of organs such as the kidney, liver and lung." Lichtman presented the work at the 40th Annual New Horizons in Science Briefing, sponsored by the Council for the Advancement of Science Writing, hosted by the University Oct. 27-30. "The experiences we have in the world somehow shape our brains," Lichtman added. "How this information is encoded in our nervous systems is one of the deep, fundamental questions of neurobiology." To help answer that question, Lichtman, Joshua R. Sanes, Ph.D., the Alumni Endowed Professor of Neurobiology, and other colleagues in the School of Medicine, have developed strains of mice with nerve tracts stained with up to four different fluorescent jellyfish proteins, each of which glows with a different color when exposed to the correct energy of light. Using an advanced technology such as low-light-level digital imaging, confocal microscopy and two-photon microscopy, the investigators can observe over time nerve cells and the synapses that interconnect them within the brain. Two-photon microscopy uses a powerful infrared laser that can selectively stimulate the fluorescent proteins in the nerve cells deep within the brain to glow. This approach permits imaging the brain without having to penetrate the skull. Computerized techniques then produce 3-D images of neural connections in the living animal, enabling researchers to watch how patterns of connections between neurons change during learning and development. The researchers' studies are providing fascinating clues about how learning occurs in the brain. For instance, it seems that nerve cells in the brain begin with many connections to other nerve cells. With time, many of these connections are eliminated shortly after birth. "The brain begins with many diffuse and unspecialized sets of connections and then sort of sculpts out subsets of those connections to serve particular functions," Lichtman said. "In essence, it seems that as we improve at some things, we lose our ability for other things."

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