A Multimodal Multidimensional Map of the Mouse Brain

Toga, Arthur

Abstract

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.