| Summary: | Understanding neurophysiological phenomena underlying complex mental and neurological conditions demands tools capable of delivering and receiving a diversity of neuronal signals over an extended period of time. Fiber drawing enables the fabrication of biocompatible multifunctional flexible fibers that record and modulate neural activity. However, constraints on the thermomechanical properties of materials have prevented the fiber integration of metals and low-loss polymer waveguides for concurrent electrical and optical neuromodulation. To address this challenge, three fabrication approaches based on fiber drawing were introduced. Each method delivered multifunctional probes featuring a low-loss transparent waveguide for optical stimulation, low-impedance metallic electrodes for electrophysiological recording, and a microfluidic channel for drug delivery. These probes successfully recorded optically evoked and spontaneous neural activity in mice for several weeks and were shown to be compatible with a mechanical microdrive for depth-specific recording, and with magnetic resonance imaging for anatomical and functional imaging studies. The multifunctionality of the probe was then leveraged to enable the translation of photopharmacology, a method that attaches optical switches to chemicals or proteins, to in vivo experiments. This approach enabled the reversible optical control of place preference behavior in freely moving mice. Finally, a fiber-based closed-loop neuroprosthesis was developed to bidirectionally interface with the gastrointestinal tract of swine. It was shown to successfully modulate the musculature to generate coordinated peristaltic waves and address dysmotility in the esophagus and the stomach. Taken together, the findings of this thesis are anticipated to provide a platform for multifunctional fiber-based probes development, and their application in the brain and peripheral circuits as investigational tools and therapeutic devices.
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