A multifunctional fiber platform for wireless, volumetric imaging and modulation of neural activity in vivo - Project Summary/Abstract Technologies for capturing multi-faceted neural signals underlying brain communication stand to improve our understanding of these complex pathways, which can be leveraged to better diagnose and treat neurological disorders and diseases. Such signals may be electrical or chemical in nature, originate in single neurons and propagate through entire networks, and occur on sub-millisecond timescales yet persist for days to weeks. To maximize downstream clinical impact, effective neuromonitoring tools should offer multimodal sensing and stim- ulation capabilities with high spatiotemporal resolution, while chronically recording from large neuronal popula- tions, and minimally perturbing animal physiology and behavior. This proposal seeks to fulfill these needs by equipping thin, polymer-based multifunctional fibers with optical imaging capabilities and coupling them to wireless recording devices. Existing endoscopic optical imaging tools, which use implanted lenses to visualize neural activity via genetically-encoded fluorescent indicators, can record from greater numbers of spatially-distinct neurons than electrophysiological methods, and detect complementary information to neuronal firing, such as neurotransmitter release. However, these tools lack direct electrical and chemical stimulation and recording abilities, and may provoke foreign body response, limiting long-term use in vivo, especially in deep brain circuits. Alternatively, multifunctional fibers for electrical, chemical, and optical interrogation of localized brain regions exhibit stronger materials compatibility with tissue due to their softer sub- strates and smaller diameters, enabling chronic usage. Although these devices have previously only offered opportunities for bulk optical recordings, this work will integrate polymer fiber waveguide bundles to achieve spatially-resolved images, while preserving small device footprint, low stiffness, and multifunctionality. We will leverage light field signal processing to transform fiber bundle images into 3D volumes, captured by a head- mounted device featuring hardware for dual-wavelength imaging and fully wireless data transmission and real- time control. We will deploy our fully-untethered devices to study firing and neurotransmitter dynamics in re- sponse to social interactions in the mesolimbic pathway, a deep brain circuit implicated in stress, motivation, and social dysfunction. These experiments will highlight our ability to complementarily expand the aspects of neural activity able to be captured, as well as the experimental paradigms under which such recordings are feasible. This work will benefit strongly from the multidisciplinary training environment at the Massachusetts Institute of Technology through access to key technical resources provided by the Materials Science, Electrical Engineering, and Brain and Cognitive Science departments, which will be critical to developing the proposed devices. Addi- tional intellectual and career development resources offered by mentored and independent training programs will further strengthen technical foundations and offer necessary preparation for future independence in this field.
