The CIC, home of the Mouse Connectome Project (MCP) seeks to develop a multimodal multiscale connectome and cell-type map of the mammalian brain using advanced tracing, imaging, and computational methods.
Our crossdisciplinary group develops neuroanatomic and neuroinformatic approaches to understand connectivity patterns in both health and disease.
The Mouse Connectome Project (MCP) is an NIH-funded project that aims to create a complete mesoscale connectivity atlas of the C57Black/6 mouse brain and to subsequently generate its global neural networks. This will help researchers gain a better understanding of how different brain structures organize into networks and how they communicate with one another to influence behavior. Multiple fluorescent neural dyes are used to trace all of the connections of the roughly 800 identified structures of the mouse brain. Novel computational neuroinformatics tools, developed through the collaborative efforts of MCP neuroanatomists and computer scientists, are used to quantify and analyze the large-scale datasets, to extract the valuable information embedded in the terabytes of acquired image data.
The MCP team is comprised of a blend of neuroanatomists, computer scientists, and web programmers each with a complementary set of skills that facilitates our multi-disciplinary approach to computational neuroanatomy.
The MCP site offers a catalog of neural tracer injection cases, which are updated continuously and eventually will cover the entire brain. Serial sections of each case are available to view at 10x magnification in the interactive iConnectome viewer. Currently, 305 cases, consisting of 675 injection sites and 1137 pathways, are available to explore in iConnectome. Each case is comprised of multiple channels: several channels for each of the variety of tracers used in the individual cases (i.e., PHAL, BDA, FG, CTb-647, 488, 549, AAV-GFP, AAV-RFP; see Methodology), one for the brightfield Nissl background, and a final channel for the corresponding Allen Reference Atlas (ARA) level of the sections. Each layer can be turned on, off, or adjusted for transparency to overlay different tracer labels with the Nissl and/or the ARA background.
The MCP website also features connectivity maps, which contain graphic reconstructions of the labeling produced by the tracer injections atop a standard mouse brain atlas. These maps provide a fast and easy way to view and compare projection patterns across injections. In the map viewer, raw data from different cases have been graphically rendered into individual layers within the neuroanatomic frame of the Allen Reference Atlas (ARA). This allows users to directly compare input and output characteristics of different regions by simply selecting the layers that contain labeling for their regions of interest. Currently, our cortico-cortical and cortico-striatal connectivity maps are available for viewing. Additional connectivity maps are continuously being produced and will be made available in the near future. Launch iConnectome maps.
Identifying classes of neural cell types will pave the way for researchers to selectively manipulate circuits and develop cell-type specific therapeutics for neurological diseases. Accurately classifying cell types requires an understanding of multiple neuronal properties including neuromorphology, connectivity, and gene expression. The CIC's multimodal approach will enable creation of the first-ever cell-type map of the mouse brain. Defining cell types is supported by NIH/NIMH RF1MH114112 (Hong-Wei Dong, Long Cai, Li Zhang); NIH/NIMH U01MH114829 (Hong-Wei Dong, Giorgio Ascoli, Byungkook Lim); NIH/NIMH U19MH114821 (Josh Huang, Paola Arlotta); NIH/NIMH U19MH114831 (Joseph Ecker, Edward Callaway). Learn more
The first challenge involved in building a connectome is to produce and collect vast amounts of connectivity data. The secondary challenge lies in accurately analyzing the large-scale datasets to convert laboratory data into useable knowledge and to intuitively visualize the conclusions. As such, the MCP develops novel informatics tools for data analysis and visualizations. Details regarding our informatics workflow and visualizations are provided in our publications. Go to Connectome data or Publications.
Research now shows that disconnections in the brain underlie manifestations of symptoms for disorders including Huntington’s disease, Parkinson’s disease, Alzheimer’s disease, autism spectrum disorders and many others. Therefore, it is important to identify the precise locations of these disconnections to constrain research regarding these disorders to specific regions of the brain. The MCP team applies the connectomics approach to mouse models of different disorders to localize these connectional disruptions. Our recent findings for such pathological connections in Huntington’s disease and autism spectrum disorders is detailed in a recent publication. Go to Connectome data or Article.
The CIC at USC is a collaborative environment hosting scientists from backgrounds ranging from neuroanatomy, to microscopy and computer science, facilitating the production, collection, and analysis of brain-wide connectivity data. The CIC has also established collaborations with institutions outside of USC, as part of an integrated effort to identify and define the neural networks and cell types of the mammalian brain. Academic partners include renowned scientists across the US from a variety of backgrounds: geneticists who create specialized viral circuit tracers, engineers who develop cutting edge imaging technologies, and experts in the field of human disorders including Alzheimer’s and Huntington’s Disease are part of this effort.