Imaging Cells during Behavior Core

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PROJECT SUMMARY: Imaging Cells during Behavior Core Addiction is a chronic, relapsing disorder due to perturbations in neural circuits. To better understand the underlying pathophysiological processes occurring in addiction and the actions of new therapies, there are pressing needs to monitor neural activity and structure during addiction and relapse. Visualization of nervous system function and structure in the intact, behaving animal is a powerful approach to meet these needs. Recent advances in genetically encoded Ca2+ indicators and imaging instruments have greatly expanded the opportunities for imaging the nervous system at work. Concurrently, there is a revolution in the use of high-speed video cameras combined with sophisticated computational tools to monitor and quantify behavior. Many labs at the University of Minnesota (UMN) lack the equipment and expertise to perform neural imaging during behavior. Nor is it possible for most investigators to keep up with the rapid changes in optical tools, either in the engineering or application domains. The Imaging Cells during Behavior Core (ICBC) is designed to allow addiction researchers and the wider neuroscience community access to modern techniques to image brain function and structure during behavior. Providing up-to-date imaging techniques, engineering and manufacturing support, as well as computational tools, will not only reduce the time and costs needed to set up experiments and process data, but also lower the entry barriers for both new and established investigators. The ICBC’s engineering, experimental, and analytical expertise will allow labs to be at the forefront of imaging technology. Aim 1 is to provide resources, expertise and training in three in vivo imaging technologies used in behaving animals: 1) head-mounted miniaturized microscopes for cellular level imaging at the surface and in deeper brain structures; 2) wide field-of-view (FOV) imaging of the cerebral cortex at both the mesoscopic and cellular levels; and 3) fiber photometry to monitor the activity of genetically defined elements in neural circuits. UMN investigators deemed these technologies critical to understanding how neural circuits change in addiction. The ICBC will provide sophisticated hardware and software to monitor and analyze behavior in head-fixed and freely moving animals and the engineering and analytical expertise to build and use these in vivo imaging technologies. Aim 2 extends and adds new imaging capabilities. Many UMN addiction researchers use rats, but most neural imaging techniques were developed for mice. Therefore, we will extend our imaging tools to the rat. In addition, Aim 2 will combine fiber photometry with wide FOV cortical imaging, enhance wide FOV imaging to access deeper cortical structures, and make wide FOV imaging compatible with magnetic resonance imaging. ICBC personnel will work closely with investigators to employ these improvements to advance their research programs. In summary, the ICBC will provide the research infrastructure, expertise and training to allow neuroscientists to image neuronal activity and neural circuitry during behavior. Providing these tools will enhance the productivity, quality, and impact of addiction-related and neuroscience research in general at the UMN.