A platform for innovation in miniature microscopy

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Miniature head-mounted fluorescence microscopes allow neuroscientists to record from populations of neurons longitudinally at cellular resolution in freely moving animals. However, off-the-shelf devices currently lack a number of desirable features such as easy modification, wireless interfacing, and flexible real-time analysis software. This project will disseminate an open-source miniature microscope (“miniscope”) that meets these needs. New features realized in the miniscope include a 3D-printed housing for easy microscope reconfiguration, wireless telemetry, and color CMOS sensors for simultaneous recording of multiple fluorescence indicators. In addition to the microscope, this project disseminates open-source software for controlling the microscope. This software is capable of real-time image processing and feedback for closed-loop experiments that trigger stimulation or other events in response to patterns of recorded neural activity. The strategy for dissemination is two-fold. First, the project provides fully functioning miniscopes and associated components and training for 14 collaborating labs. These end-users will use the microscopes to address a wide range of questions in surface and deep brain nuclei, focused on many distinct cell types. These groups will study learning in normal brain functioning and pathological activity patterns in multiple disease models. Second, the project will create a public web repository containing resources and documentation necessary to reproduce the microscope in other laboratories. Finally, the project will implement a number of design variations requested by end-users. These design variations include changes in the field of view, specialized microscope housings, adaptations for simultaneous electrophysiology, new color imaging strategies, and user-defined changes to the real-time software. These design variations will also be described in the public web resources. Ultimately, the goal of the project is to provide a platform for innovation in the use of customized miniature microscopes.