Project Summary: The main goal of this research project is to develop a new line of new stereotaxic devices for small animal research that outperforms existing devices in terms of accuracy, reproducibility, and ease of use. Advancing a tool such as an electrode, injection pipette or optical fiber through a small hole in the cranium, sometimes over long distances, and placing it precisely in a particular brain area, often much less than one millimeter in diameter, is a significant experimental challenge. Any time an investigator misses the target brain area and the experiment fails as a result, a significant amount of work is lost, additional animals get sacrificed, materials are wasted, and the pace of scientific discovery has been slowed. Even in cases when experiments succeed, they can be difficult to reproduce because many research groups rely on their most experienced lab members and their “special touch” to perform these procedures – thereby adding an element of non- quantitativeness to the procedures, effectively making the experiment less reproducible. We propose to develop a novel stereotaxic apparatus which will overcome many of these shortcomings. Our device features a radically different mechanical design which is natively compatible with both traditional and novel in-vivo techniques. We propose to combine computer 3D vision and robotics for automatic and software guided adjustments of the animal's skull. Landmarks are measured with 3D vision, based on structured illumination at a level of accuracy that has not been accomplished by any of the existing devices. This information will guide a robotic platform to position the animal for the experiment. Finally, we propose to develop an open software platform for neuronavigation that will allow investigators to use the platform with any small animal species they desire to use. Brain atlas systems for neuronavigation can either be downloaded from a cloud based site, or produced de-novo by the investigator by preparing a single set of MRI and CT scans from one sample animal. Our device will help make stereotaxic procedures more accurate and less dependent on human input and thereby increase the repeatability of experiments within a laboratory as well as the reproducibility of experiments across laboratories.