The Development of Tabletop Brain-Mapping Platform

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PROJECT SUMMARY Central Nervous System (CNS) disorders place an enormous burden on society and have proven to be among the most challenging areas for which to develop a therapeutic. A major reason for this is that the brain is a complex, 3D, multiscale organ, with a heterogenous distribution of components across hundreds of brain regions. Extensive BRAIN Initiative efforts are underway to map this complexity by conducting surveys of connectivity pattern and cells types. Digital brain atlases such as the Allen Mouse Brain CCF v3.0 have become essential tools in organizing the results of these endeavors. The availability of the Allen CCFV3.0 and whole-brain surveys are transforming CNS studies. However, brain mapping still too frequently requires access to expensive equipment, specialized techniques, and dedicated personnel. Moreover, many newer techniques are incompatible with established histology protocols, which severely limits the contribution of foundational techniques to brain mapping efforts. In addition, the tedious manual production of slides remains a significant obstacle to high throughput histology. These difficulties present a significant barrier to the field and hinders progress in understanding the CNS. This proposal will remove these barriers by developing an affordable, table-top hardware and software mouse brain imaging and tissue processing platform accessible to the non-specialist neuroscience lab. It is based on the proven microtomy, section capture, and slide mounting technology contained in TissueVision's commercially successfully state-of-the-art multiphoton- based TissueCyte platform. This proposal will extend the capabilities of our current system and extend it to sections as thin as 15 microns and replace the TissueCyte's advanced multiphoton imaging with less expensive block-face imaging. In Phase II we will be package the integrated tissue processing technology into a convenient, compact instrument. This table-top, affordable device will combine the ease of working from 2D sections with the power of 3D brain analyses and help propel forward the development of new therapeutics. This product will be brought to market by a team of world-class experts at TissueVision who have successful commercialization experience in instrumentation for high throughput histology and brain mapping. We will be aided by a superb network of partners in leading neuroscience labs who will beta test the product and provide crucial feedback in Phase II to ensure a successful product launch and acceptance into the marketplace.