One of the great challenges in neuroscience is to understand how the neurons of the brain work together as a circuit to compute behaviors, and how such circuit functions are changed in brain disorder states. There is a great need for technologies that enable the neural activity of large numbers of individual cells to be measured in the brain of a mammal such as a mouse - ideally throughout the entire brain, since we do not precisely know the exact set of cells involved with any behavior or brain disorder. We here propose two radical departures from the past, using computational and theoretical analyses to design new neural recording devices, and augmenting these technologies with supplementary tools to enable the bridging of dynamic and anatomical pictures of the brain. As we validate these technologies, we will examine whole-brain neural dynamics and anatomical phenotypes in autism and schizophrenia mouse models, performing whole-brain activity mapping to characterize the altered computations associated with psychiatric illness. Such maps may fundamentally open up new frontiers in thinking about how distributed brain circuits are changed in mental illness, paving the way to new treatment strategies.

Public Health Relevance

The brain is a three-dimensional, densely wired circuit made of cells which interact at a fast timescale. I propose to develop a set of technologies that enable an analysis of how neurons distributed throughout the entire brain compute to implement behavior, and how these interactions go awry in brain disorders. This ability to map such widespread neural dynamics will yield new and fundamental principles of how neural circuits compute, and these technologies will also enable scientists and clinicians to develop new, efficacious, side-effect free treatments to confront the spectrum of neurological and psychiatric disorders. THE FOLLOWING RESUME SECTIONS WERE PREPARED BY THE SCIENTIFIC REVIEW OFFICER TO SUMMARIZE THE OUTCO

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
NIH Director’s Pioneer Award (NDPA) (DP1)
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Special Emphasis Panel (ZRG1-BCMB-N (50))
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Ludwig, Kip A
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Massachusetts Institute of Technology
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United States
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