Research Project
8336763
Genetically modified animal models, such as the zebrafish, are frequently employed to understand the development, genetics, and biological processes associated with human diseases. To decipher the complex genotype-phenotype relationships underlying inherited neurological disorders, the structure of the central nervous system in a transgenic model must be compared with that of wild-type animals. Anatomical methods that rely on transparency of the zebrafish are restricted to embryonic and larval animals but cannot be applied to older animals (> 6 days post fertilization), which have become opaque. Moreover, results obtained with this immature age group may not be applicable for neurodegenerative diseases with a mid- to late-life onset. Consequently, there is a growing interest in the use of mature-aged (juvenile and adult) zebrafish in studies of neurodegenerative diseases. However, a complete anatomical characterization of the mature zebrafish brain and a quantitative voxel-based probabilistic map of brain structures are needed to compare disease models with wild-type zebrafish. Recent technological developments in magnetic resonance imaging (MRI) now enable non-invasive and three-dimensional imaging of the juvenile and adult zebrafish brain. Specifically, with high- resolution T2*-weighted and super-resolution track density imaging, delineations of gross brain regions and white matter tracts are now possible at resolutions better than 10¿m isotropically. Therefore we propose (1) to develop a probabilistic atlas of the wild-type (AB) zebrafish brain with high resolution T2*-weighted and super- resolution track density imaging (TDI); (2) to reconstruct histological specimens of the brain into three- dimensional volumes and to co-register these with the MR images allowing cross-referencing across modalities; (3) to create a tractographic atlas using seed points within brain regions segmented in Aim 1.
