This is a project to develop a detailed multidimensional digital atlas of the mouse nervous system. It will, for the first time, create a unified framework for representing brain maps and gene expression maps. The creation of a comprehensive framework to encompass diverse imaging and genetic information about the mouse holds tremendous promise for integrating the genotype and phenotype of this animal. This work is significant because a comprehensive description of geno- and phenotypic patterns and how they relate to the emerging morphology is crucial to our understanding of the interactions that underlie the processes of development, normal structure and function, disease and evolution. This proposal describes an ambitious project coordinated between three leading imaging centers that will combine genetic, in vivo and post mortem maps in a multidimensional digital atlas of the mouse brain. This interactive atlas will contain information from structural and diffusion-weighted microscopic magnetic resonance imaging (uMRI), metabolic studies derived using positron emission tomography (PET), high resolution cryosection imaging as well as multiple histological and in situ hybridization experiments. Comprised of many subjects collected across the development of the C57BL/6J mouse from early embryonic through adult stages and analyzed using sophisticated four- dimensional warping algorithms, this atlas will form the basis of a detailed space-time reference system. The atlas will combine genetic, anatomical and functional data for intermodality, interspecies, and cross-laboratory comparisons. In addition to the unified datasets comprising the atlas itself, this project will result in multiplatform software tools facilitating its interactive exploration and augmentation. The specific goals of this project are: 1. To develop and implement a fundamental anatomic framework to map gene expression in the brain. 2. To create a set of tools to co-localize data from different markers, animals and laboratories. 3. To disseminate the atlas and requisite interactive tools, enabling output (ability for others to use information/data) and input (ability to incorporate and correlate data from other sources). In addition to these design driven goals, we will test for hypothesis during the process of validation and evaluation of the atlas. 1. There is a relationship between gene expression and morphology. 2. Patterns of gene expression co-vary with morphological changes during development. 3. Anatomy from histological delineations accurately represents in vivo morphology. 4. At any maturational stage, within strain morphometric variability will be less than between strains. The resulting validated, multimodality, multidimensional mouse atlas will have immense value for studying normal, mutant, healthy and diseased animals in a wide range of neuroscientific investigations.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (ZMH1-BRB-I (02))
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Huerta, Michael F
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University of California Los Angeles
Schools of Medicine
Los Angeles
United States
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Bota, Mihail; Swanson, Larry W (2007) The neuron classification problem. Brain Res Rev 56:79-88
Mackenzie-Graham, Allan J; Lee, Erh-Fang; Dinov, Ivo D et al. (2007) Multimodal, multidimensional models of mouse brain. Epilepsia 48 Suppl 4:75-81
Tyszka, J Michael; Readhead, Carol; Bearer, Elaine L et al. (2006) Statistical diffusion tensor histology reveals regional dysmyelination effects in the shiverer mouse mutant. Neuroimage 29:1058-65
Martin, Melanie; Hiltner, Timothy D; Wood, John C et al. (2006) Myelin deficiencies visualized in vivo: visually evoked potentials and T2-weighted magnetic resonance images of shiverer mutant and wild-type mice. J Neurosci Res 84:1716-26
Tyszka, J Michael; Ewald, Andrew J; Wallingford, John B et al. (2005) New tools for visualization and analysis of morphogenesis in spherical embryos. Dev Dyn 234:974-83
Bota, Mihail; Dong, Hong-Wei; Swanson, Larry W (2005) Brain architecture management system. Neuroinformatics 3:15-48
MacKenzie-Graham, Allan; Lee, Erh-Fang; Dinov, Ivo D et al. (2004) A multimodal, multidimensional atlas of the C57BL/6J mouse brain. J Anat 204:93-102
Pautler, Robia G; Mongeau, Raymond; Jacobs, Russell E (2003) In vivo trans-synaptic tract tracing from the murine striatum and amygdala utilizing manganese enhanced MRI (MEMRI). Magn Reson Med 50:33-9
MacKenzie-Graham, Allan; Jones, Eagle S; Shattuck, David W et al. (2003) The informatics of a C57BL/6J mouse brain atlas. Neuroinformatics 1:397-410
Toga, Arthur W (2002) The Laboratory of Neuro Imaging: what it is, why it is, and how it came to be. IEEE Trans Med Imaging 21:1333-43

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