Transforming brain research with jellyfish genes and advances in microscopy

Researchers at Washington University School of Medicine in St. Louis are transplanting jellyfish genes into mice to watch how neural connections change in the brains of entire living animals. The development represents the merging of several technologies and enable researchers to watch changes inside living animals during normal development and during disease progression in a relatively non-invasive way.

“This work represents a new approach to studying the biology of whole, living animals,” says 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, held Oct. 27-30 at Washington University in St. Louis.

“The experiences we have in the world somehow shape our brains,” says Lichtman. “How this information is encoded in our nervous systems is one of the deep, fundamental questions of neurobiology.”

To help answer that question, Lichtman, together with Joshua R. Sanes, Ph.D., Alumni Endowed Professor of Neurobiology, and other colleagues at the School of Medicine, have developed strains of mice with nerve tracts stained by 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 within 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 three-dimensional images of neural connections in the living animal, enabling the 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 example, 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,” says Lichtman. “In essence, it seems that as we improve at some things, we lose our ability for other things.”

Questions

Contact: Darrell E. Ward, assc. director for research communications, Washington University School of Medicine, (314) 286-0122; wardd@msnotes.wustl.edu