We propose to design, build, apply, and disseminate a device that will push the boundaries of current technology for volumetric imaging of distributed activity of large-scale neuronal circuits at high neuronal sampling rate and single cell resolution. The proposed technology will enable unbiased Ca2+ imaging of unprecedentedly large cortex-wide volumetric fields of views (V-FOV) of ~5x5x0.8mm at multi-Hertz time resolution in behaving rodents and marmosets. We will be able to image neuronal population activity from ~2 million neurons distributed across cortex in 3D in awake behaving animals. This capability will allow capturing functional organization, activity patterns, and correlation-structure of neuronal population dynamics within and across layers of the mammalian cortex and thus provide an unprecedented opportunity to gain fundamentally new mechanistic insights into the computational principles of neural information processing. To achieve this goal, our imaging system will synergistically integrate and combine light-field microscopy (LFM), new mathematical algorithms for signal demixing with multiplexed and patterned excitation schemes leveraging compressed sensing strategies within a large field of view. To effectively disseminate this technology, we will use two complementary platforms: an open access web platform through which we will provide detailed technical information, including software and support for technologically advanced users. In addition we have established a strategic partnerships with industrial partners through whom we will disseminate our imaging modules and software to the broader neuroscience community. Our modules can be interfaced with various other existing platforms. Our technologies will be iteratively optimized through closed loop interactions between our lab with the end user neuroscience labs at The Rockefeller University and other partner institutions. !

Public Health Relevance

Understanding how brain-wide activity of neural networks in the brain leads to cognitive functions and behavior is a central goal of neuroscience, and is relevant for public health, because it is essential for understanding neurological and psychiatric disorders. Success hinges critically upon the availability of technologies that enable the simultaneous recording from very large number of neurons that form functionally relevant circuits. The proposed research will address this critical need by designing, building, applying, and disseminating a new optical imaging system that enables functional recordings from nearly 2 million neurons distributed across the mammalian cortex in behaving animals, thereby enabling a major leap forward in the understanding of fundamental principles of neural information processing supporting cognitive function.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZNS1)
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Talley, Edmund M
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Rockefeller University
Graduate Schools
New York
United States
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Weisenburger, Siegfried; Vaziri, Alipasha (2018) A Guide to Emerging Technologies for Large-Scale and Whole-Brain Optical Imaging of Neuronal Activity. Annu Rev Neurosci 41:431-452