Abstract
The thorough characterization of transgenic mouse models of human central nervous system diseases is a necessary step in realizing the full benefit of using animal models to investigate disease processes and potential therapeutics. Because of the labor- and resource-intensive nature of high-resolution imaging, detailed investigation of possible structural or biochemical alterations in brain sections has typically focused on specific regions of interest as determined by the researcher a priori. For example, Parkinson's disease researchers often focus imaging on regions of the brain expected to exhibit pathology such as the substantia nigra and striatum. Because of limitations in acquiring and storing high-resolution imaging data, additional data contained in the specimen is not usually acquired or disseminated/reported to the research community. Here we present a method of imaging large regions of brain at close to the resolution limit of light microscopy using a mosaic imaging technique in conjunction with multiphoton microscopy. These maps are being used to characterize several genetically modified animal models of neurological disease by filling the information “gap” among techniques such as magnetic resonance imaging and electron microscopic analysis.
Similar content being viewed by others
References
Bestvater, F., Spiess, E., Stobrawa, G., et al. (2002) Two-photon fluorescence absorption and emission spectra of dyes relevant for cell imaging. J. Microscopy 208(2), 108–115.
Bobik, M., Ellisman, M. H., Rudy, B., and Martone, M. E. (2004) Potassium channel subunit Kv3.2 and the water channel aquaporin-4 are selectively localized to cerebellar pinceau. Brain Res. 1026(2), 168–178.
Bohm, J., Frangakis, A. S., Hegerl, R., Nickell, S., Typke, D. and Baumeister, W. (2000) Toward detecting and identifying macromolecules in a cellular context: template matching applied to electron tomograms. Proc. Natl. Acad. Sci. USA 97(26), 14,245–14,250.
Bouwer, J. C. (2002) Preparation, Theory, and Biological Applications of Highly Luminescent CdSe/ZnS Quantum Dots in Optical and Electron Microscopy. Ph.D. Thesis, University of California, San Diego, La Jolla, CA.
Brevik, A., Leergaard, T. B., Svanevik, M., and Bjaalie, J. G. (2001) Three-dimensional computerised atlas of the rat brain stem precerebellar system: approaches for mapping, visualization, and comparison of spatial distribution data. Anat. Embryol. (Berl.) 204(4), 319–332.
Bushong, E. A., Martone, M. E., Jones, Y. Z., and Ellisman, M. H. (2002) Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains. J. Neurosci. 22(1), 183–192.
Chow, S. K., et al. Automated Microscopy System for Mosaic Acquisition and Processing, (submitted).
Fan, G. Y., Fujisaki, H., Miyawaki, A., Tsay, R. K., Tsien, R. Y., and Ellisman, M. H. (1999) Videorate scanning two-photon excitation fluorescence microscopy and ratio imaging with cameleons. Biophys. J. 76(5), 2412–2420.
Gong, S., Zheng, C., Doughty, M. L., et al. (2003) A gene expression atlas of the central nervous system based on bacterial artificial chromosomes. Nature 425(6961), 917–925.
Harlow, M. L., Ress, D., Stoschek, A., Marshall, R. M., and McMahan, U. J. (2001) The architecture of active zone material at the frog's neuromuscular junction. Nature 409(6819), 479–484.
Jellinger, K. A. (2003) Neuropathological spectrum of synucleinopathies. Movement Disord. 18, S6, S2–S12.
Johnson, G. A., Cofer, G. P., Gewalt, S. L., and Hedlund, L. W. (2002a) Morphologic phenotyping with MR microscopy: the visible mouse. Radiology 222(3), 789–793.
Johnson, G. A., Cofer, G. P., Fubara, B., Gewalt, S. L., Hedlund, L. W., and Maronpot, R. R. (2002b) Magnetic resonance histology for morphologic phenotyping. J. Magn. Reson. Imaging 16(4), 423–429.
Lieberman, B. (2004) Abrainstorming hub: San Diego now a world center for research in neuroscience. San Diego Union Tribune, p. 61, October 22.
MacKenzie-Graham, A., Jones, E. S., Shattuck, D. W., Dinov, I. D., Bota, M., and Toga, A. W. (2003) The informatics of a C57BL/6J mouse brain atlas. Neuroinformatics 1(4), 397–410.
Martone, M. E., Gupta, A., and Ellisman, M. H. (2004) E-neuroscience: challenges and triumphs in integrating distributed data from molecules to brains. Nat. Neurosci. 7(5), 467–472.
Martone, M. E., Jones, Y. Z., Young, S. J., Ellisman, M. H., Zivin, J. A., and Hu, B. R. (1999) Modification of postsynaptic densities after transient cerebral ischemia: a quantitative and three-dimensional ultrastructural study. J. Neurosci. 19(6), 1988–1997.
Martone, M. E., Gupta, A., Wong, M., et al. (2002) A cell-centered database for electron tomographic data. J. Struct. Biol. 138(1,2), 145–155.
Martone, M. E., Zhang, S., Gupta, A., et al. (2003) The cell-centered database: a database for multiscale structural and protein localization data from light and electron microscopy. Neuroinformatics 1(4), 379–395.
Masliah, E., Rockenstein, E., Veinbergs, I., et al. (2000) Dopaminergic loss and inclusion body formation in alpha-Synuclein mice: implications for neurodegenerative disorders. Science 287, 1265–1269.
May, M. (2004) Linux in the Lab: Mixing computational power with a raw hacker's edge the open-source operating system gains ground, Scientist 18, 21–24.
McEwen, B. F. and Frank, J. (2001) Electron tomographic and other approaches for imaging molecular machines. Curr. Opin. Neurobiol. 11(5), 594–600.
Medalia, O., Weber, I., Frangakis, A. S., Nicastro, D., Gerisch, G., and Baumeister, W. (2002) Macromolecular architecture in eukaryotic cells visualized by cryoelectron tomography. Science 298(5596), 1209–1213.
Nisman, R., Dellaire, G., Ren, Y., Li, R., and Bazett-Jones, D. P. (2004) Application of quantum dots as probes for correlative fluorescence, conventional, and energy-filtered transmission electron microscopy. J. Histochem. Cytochem. 52(1), 13–18.
Paxinos, G. and Franklin, K. B. J. (2000) The Mouse Brain in Stereotaxic Coordinate, 2nd ed. Academic Press, San Diego.
Peltier, S. T., Lin, A. W., Lee, D., et al. (2003) The telescience portal for advanced tomography applications. J. Parallel Distributed Appl, Special Edition on Computational Grids 63(5), 539–550.
Price, D. L., Chow, S. K., Hakozaki, H., et al. (2004) Application of a multiphoton high-resolution large-scale montage imaging technique to characterize transgenic mouse models of human neurodisorders. Microsc. Microanal., Abstract, Annual Meeting Savannah, GA.
Rockenstein, E., Mallory, M., Hashimoto, M., et al. (2002) Differential neuropathological alterations in transgenic mice expressing alpha-synuclein from the platelet-derived growth factor and Thy-1 promoters. J. Neurosci. Res. 68(5), 568–578.
Russ, B. (1999) The Image Processing Handbook. Boca Raton, Florida: LLC, CRC Press.
Stafford, J. (2004) Rocks Linux and Sun desktops ‘supersize’ scientists images. Search Enteprise Linux.com.
Wang, Y., Santini, S., and Gupta, A. (2005) Efficiently Querying Spatial Histograms. Storage and Retrieval Methods and Applications for Multimedia. Proceedings of the SPIE-IS&T Electronic Imaging. SPIE 5682, 183–194.
Wolberg, G. (1990) Digital Image Warping, IEEE Computer Society Press, Los Alamitos, CA, pp. 70–75.
Zerhouni, E. A. (2003a) A new vision for the national institutes of health. J. Biomed. Biotechnol. 3, 159, 160.
Zerhouni, E. A. (2003b) Medicine. The NIH Roadmap. Science 302(5642), 63–72.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Price, D.L., Chow, S.K., MacLean, N.A.B. et al. High-resolution large-scale mosaic imaging using multiphoton microscopy to characterize transgenic mouse models of human neurological disorders. Neuroinform 4, 65–80 (2006). https://doi.org/10.1385/NI:4:1:65
Issue Date:
DOI: https://doi.org/10.1385/NI:4:1:65