A population-bases atlas of the zebrafish brain for quantitative phenotypic compa -
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.