A group of experienced neuroscientists will closely interact to provide a high throughput analysis of various aspects of brain structure and implied function. These investigators have had, as a whole, a long history in the neuroanatomic analysis of normal and mutant brain structures. They will collectively produce a high quality database, disseminated on the Internet, that will provide an integrated summary of the major aspects of brain organization in a large variety of inbred and recombinant inbred strains of mice. Three timepoints in the life history of the mouse will be assessed: embryonic day 17.5, postnatal day 60-90, and 18-24 months of age. Several features of the proposed neurohistological screen obviate time consuming methods and introduce a great deal of flexibility for phenotype assessment. Using a set of seven straightforward and reproducible staining procedures (cresyl violet, osmium tetroxide, Timm's stain, anti-glia fibrillary acidic protein and anti-NeuN immunohistochemistry, cytochrome oxidase histochemistry, cell birthdating with BrdU immunocytochemistry), the plan is to assess the cytoarchitectonics, myelinated fiber pathways, terminal fields, astroglia and neuronal populations, activity state, and proliferative populations in a extensive series of adult inbred and hybrid mice that are commonly used for neurobiological studies and transgenic experimentation. These seven procedures will produce a detailed and composite view of neural organization that will be assessed at the qualitative and quantitative levels of analysis. For embryonic and aged mice, additional stains and imaging methods will assess various hallmarks of the developing and aged brain. One important endpoint of these efforts will be to develop a relational database that can be used to compare and measure various aspects of nervous system structure. Strain differences can be readily assessed by consulting this online database. The recovery of apparent mutant phenotypes that are reflected in abnormalities in brain structure can be compared to this database. Furthermore, in collaboration with other researchers in the field, these efforts will coordinate a host of phenotypic data such as cell number, nuclear volume and density of neurons, and molecular expression patterns to begin to mine the wealth of data that is inherent in the natural and quantitative variation of traits in inbred strains of mice.
| Poon, Anna; Goldowitz, Daniel (2014) Identification of genetic loci that modulate cell proliferation in the adult rostral migratory stream using the expanded panel of BXD mice. BMC Genomics 15:206 |
| Poon, Anna; Goldowitz, Dan (2013) Effects of age and strain on cell proliferation in the mouse rostral migratory stream. Neurobiol Aging 34:1712.e15-21 |
| Poon, Anna; Li, Zhiyou; Wolfe, Gregory W et al. (2010) Identification of a Chr 11 quantitative trait locus that modulates proliferation in the rostral migratory stream of the adult mouse brain. Eur J Neurosci 32:523-37 |
