Understanding the exact cell-type composition in the different regions of the mouse brain is a fundamental step when trying to integrate physiological, behavioral, neurochemical and molecular data. At present, although major categories of cell-types present in the mouse brain have been defined through a handful of specific markers, the different subtypes within these categories, as well as their location and connectivity are far from understood. Epigenomic signatures such as DNA methylation (mC) and open chromatin are stable modifications that persist in post-mitotic cells throughout their lifetime, defining their cellular identity. Open chromatin as well as methylation patterns are cell type specific, differentiating the major types of cells i.e., neurons and glia, in the rodent and human cortex, as well as differentiating neuronal types in mouse brain. Research Segment 1 of this center proposes to produce a catalog of methylation and open chromatin patterns at the single-cell level throughout the entire mouse brain. Analysis of the combined data will permit the discovery of cell-type specific regulatory regions that will allow the production of transgenic mouse lines and viral tools that will become available to the community.

Public Health Relevance

Brain function arises from networks of cells connected to each other in neural circuits. The goal of this project is to understand the identity, location and connectivity of the many different kinds of cells that form a brain, using the laboratory mouse as a model. Determining the cell composition in various regions throughout the brain will create a detailed atlas that will aid in the understanding of a variety of human diseases where these neural circuits may be abnormal.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Program--Cooperative Agreements (U19)
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Yao, Yong
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Salk Institute for Biological Studies
La Jolla
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Luo, Liqun; Callaway, Edward M; Svoboda, Karel (2018) Genetic Dissection of Neural Circuits: A Decade of Progress. Neuron 98:865
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