Joe Tsien - US grants

The aim of this project is to map neural circuits and their activities in the mouse brain, from the small scale level of the synapse to the neurons involved, their larger circuits, up to overall neural systems. Different data modalities will be merged in order to carry out this integration. Mapping the brain can mean showing the layout of anatomical features, showing where functional connections occur, or both, as for this project. Different features require different data collection modalities, and merging these different types of data correctly is one of several technically challenging tasks this research will perform. This type of multiscale, multimodal brain mapping is one of the scientific Grand Challenges, as such it is a top U.S.A. research priority, one recognized by the BRAIN initiative. This award will contribute to NSF's commitment to develop a National Brain Observatory (NBO) to enable this initiative. By integrating structural and functional connectomics, this project will show how they work together when brain circuits change with different activities. By deciphering and measuring of real-time neural codes this research will let us better understand how brain activities create unique cognitive and behavioral capabilities. The project includes plans to integrate the research data and techniques into educational and outreach activities, encouraging interest in neuroscience research in the next generation of scientists.


The objective of this project is to create a multiscale, multimodal mouse connectome for better understanding of brain function. Specifically, the project aims include: 1) construct, cross-validate, fuse, and integrate multiscale multimodal mouse brain connectomes, including macro-scale mouse connectomes based on diffusion tensor imaging (DTI), Susceptibility Tensor Imaging (STI) data, and meso-scale mouse connectomes based on publicly available serial two-photon tomography data; 2) utilize multiscale structural connectomes for exploration of functional connectomics and circuitry dynamics, in particular, focusing on the fear memory system; and 3) design, develop and disseminate the structural and functional connectomics tools and resources to the brain mapping research community. To achieve the above goals, the investigators will design and apply innovative computational and informatics methodologies and approaches for multiscale mouse connectomics research. Specifically, both mesoscale and macroscale structural connectivity data will be used as follows. First, the Allen Mouse Brain Connectivity Atlas (ACA) will be used, which provides a comprehensive meso-scale mouse brain neuronal connectivity map via anterogradely traced axonal projections using serial two-photon tomography from over one thousand different injection sites. Second, at the macro-scale, the noninvasive diffusion tensor (DT) microimaging technique will be used to track global fiber connections in the whole mouse brain at the micron-scale spatial resolution. Subsequently data will be fused and integrated, to acquire the advantages of both meso-scale serial two-photon tomography data and macro-scale DT microimaging data when constructing and cross-validating multi-scale, multimodal mouse connectomes. Finally, these structural connectomes will be the basis for exploring functional connectomics and circuitry dynamics, thus significantly advancing the understanding of brain structure and function and their relationships. All of these structural and functional connectomics tools will be released to the brain science community at the project website: http://mbm.cs.uga.edu/