Brain Registration and Histology

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Project Summary: Core 4, Brain Registration and Pathway Tracing    Working memory, the ability to temporarily hold multiple pieces of information in mind for manipulation, is  central to virtually all cognitive abilities. This multi-component research project aims to comprehensively  dissect the neural circuit mechanisms of this ability across multiple brain areas. The behavior to be studied is  a type of decision-making task that is based on the gradual accumulation of sensory evidence and thus relies  on working memory. A full understanding of how this behavior relates to this brain function requires  explanation at multiple levels: from neural activity in particular regions to how those regions interact in  brain-wide networks via specific pathways. These levels of analysis require distinct technical approaches,  which are often difficult to relate to one another rigorously. This Core will promote rigor and reproducibility in  the proposed research by producing an anatomical framework to standardize and compare the various types  of data that will be collected. The facility will serve several essential functions in building a broad integrative  structure for the project. First, it will produce standardized functional maps that will be used to accurately  determine the boundaries of visual cortical regions before cellular-resolution imaging or inactivation studies.  Second, it will register all studied brain areas into an anatomical context that includes connectivity and  functional significance. Automated cell-recognition methods will be used to survey directly imaged regions  and indirectly connected regions, and to classify neurons and other objects of interest. Third, it will support  long-distance tracing across synapses to identify paths of connectivity between distant brain regions involved  in evidence accumulation. Fourth, it will organize this information in a relational database that links all the  experiments, in a format that can be shared with the neuroscience research community. As technologies for  functional mapping, registration, and tracing advance over time, this facility will evaluate new methods, adopt  those that will substantially improve the Core’s capabilities, and train project personnel in their use. Taken  together, these functions are essential for placing recorded and perturbed neural activity into a brain-wide  anatomical context, which will enable the integration of information produced by individual experiments and  techniques into a coherent theoretical framework.