Timothy Otchy - US grants

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.

Abstract There is growing evidence of the therapeutic benefit of targeted modulation of electrical signaling within the network of nerves and ganglia that innervate the organs and tissues of the body (i.e., the PNS). Positive clinical trials are reported for vagal nerve stimulation to treat inflammatory diseases, depression, and epilepsy. Beyond these initial results, a broad range of chronic diseases may be treatable through precise, artificial control of the PNS. Moreover, advanced neuroprotheses hold the promise of restoring lost mobility, dexterity or sensation in the afflicted through long-term, bidirectional connection between the PNS and implantable or externalized hardware. Despite the enormous potential of these therapeutic regimes, progress ? both in basic PNS science and in developing effective interventions to improve human health ? has been hampered by the lack of tools and methods for chronically interfacing with the fine PNS targets in the small animal models in which the foundational pre-clinical research must be done. The objectives of this proposal are the development and characterization of a new peripheral nerve interface that combines soft and stretchable electrodes (Aim 1) with a nerve-anchoring technology that allows intimate, high circumferential contact with a nerve (Aim 2). We anticipate that this novel nerve interface ? the nanoclip stretchable microelectrode array (ncSMEA) ? will be highly compatible with the biomechanics of the PNS and capable of recording from and micro-stimulating small (~100-200µm diameter) peripheral nerves in pre-clinical animal models. Though this project will be focused on creating a device for electrical interfacing, this project may also inform the development of new optical, thermal, ultrasonic, or chemical interfaces that must meet similar biomechanical challenges. More generally, placing implantable probes on or nearby the soft, delicate tissues of the body is a major scientific challenge, thus we anticipate this research and technology development will impact biomedical research and implantable device development broadly. !