A broad view of a reconstructed nerve cell showing the flow of chemical signals.

Combining high-resolution serial electron microscopic tomography, neuroelectrophysiological measurements, mathematical modeling, and computer graphics, a multi-institution team led by HHMI investigator Terrence J. Sejnowski at the Salk Institute for Biological Studies has overturned a half-century's dogma in neurobiology. The researchers proved that the flow of chemical signals from nerves isn't restricted to the ends of nerve fibers, as scientists had previously believed, but that more than 90 percent of a nerve's signals emanate from parts of the cell away from the nerve terminals.

A custom-graphics program with the acronym DReAMM (Design, Render, and Animate MCell Models) gives researchers unprecedented capacity to visualize activity at the subcellular level. MCell software uses 3-D models and algorithms to simulate molecular activity within and between cells. Investigators like Terrence Sejnowski use DReAMM to design, edit, and visualize the simulations and parts of cells derived via MCell.

		View Image Membrane vesicles (green) filled with chemical signals flow toward the tip of the transmitting cell where they will cross the synaptic zone and then enter the receiving nerve cell. While the traditional view of nerve cell signaling comes from electron micrographs such as this one, more careful scrutiny has revealed that vesicles release their signaling molecules through the entire surface of the cell. Image: © Dennis Kunkel / Phototake, Inc. View Image This cross-sectional view through a junction between two nerve cells was constructed by computer-aided tomography of a thin slice of the nerve, imaged in an electron microscope. The red lines outline neurotransmitter-filled vesicles flowing from the cell that is transmitting the nerve impulse. The area above the blue line is the cell that will receive the nerve signal. View Image DReAMM renders data from many nerve cross-sections into a 3-D dynamic image of the cell. The program also superimposes mathematical modeling data describing the movements and positions of vesicles, signaling molecules, and signal receptors in the nerve tissue. View Image A close-up view of the boxed region in the previous image (above). The blackened surface shows the "postsynaptic zone," the region through which scientists had previously thought nerve signals must flow. The yellow sphere is a vesicle, green dots are neurotransmitter molecules, and the red and blue dots are two different kinds of neurotransmitter receptors. Images: (3) Reprinted with permission from Science 15 July 2005, Vol 309, pp 446-451 / © 2005 AAAS

Illustration: Thomas Bartol, Jr.