Research Highlights

3D Mouse Model Reveals Complex Structures of the Node of Ranvier

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June 2005

NCMIR researchers, in collaboration with the Salk Institute, have created a 3D model of the node of Ranvier, a complex structure found in the nervous system of higher vertebrates. The results will be published in an upcoming issue of Neuroinformatics.

Lead author Gina Sosinsky, with researchers Thomas Deerinck, Rocco Greco, Casey Buitenhuys, and Mark Ellisman of NCMIR, and Thomas Bartol of the Computational Neurobiology at the Salk Institute, examined the Nodes of Ranvier, interruptions in the myelin sheath that appear in intervals along nerve fibers and allow amplification and regeneration of action potentials. By creating a mouse model of the node of Ranvier, researchers hope to gain a better understanding of the structure-function relationship and achieve greater insight into such neurological disorders as multiple sclerosis, peripheral neuropathy, and Charcot-Marie-Tooth disease.

Recent research has shown the nodes are complex structures with multiple ionic and metabolic compartments and contain junctions of varying classes, including tight, gap, adherens, and septate-like. Because the nodes are so complex and large, it is difficult to image them in a single section using conventional electron microscopy methods. For this study, however, researchers used serial section electron tomography, a method developed at NCMIR for reconstructing cells and subcellular complexes.

Additional methods used in the study, such as the incorporation of image data and models into a computer simulation environment called MCell, reflect the increasing importance of biology in silico as a means of facilitating structure-function studies. Images such as those shown above have been deposited into Cell Centered Database (CCDB), a web-accessible database that makes 3D microscopic imaging data available to the scientific community. Animations also are available through the CCDB. According to the study, "Deposition of these reconstructions and their segmented models into the CCDB will facilitate longer range, broader structure-function studies."

The above image, a 3D tomographic reconstruction of a node of Ranvier, depicts the complete structure, including the Schwann cell membrane (yellow), compact myelin (pink), paranodal loops (magenta), and axonal membrane.