A Wireless, Multimodal Neural Probe for Simultaneous Membrane-Free Neurochemical Sampling and Neuropharmacology

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PROJECT SUMMARY/ABSTRACT Mental disorders, such as depression, anxiety, and many others, affect the quality of life of millions of people worldwide. High-molecular-weight neurochemicals, such as neuropeptides and other polypeptide neurochemicals, play critical roles in various aspects of these mental disorders. However, despite intensive work, current measurement technologies, such as microdialysis or cyclic voltammetry, lack the spatial and temporal precision and the molecular specificity to detect these larger molecules. Our long-term goal is to develop advanced tools and approaches to understand where, when, and how neuropeptide corelease modulates diverse behavioral outputs of the brain. Our immediate goal is to develop, optimize, benchmark, and fully validate a wireless, multimodal neural probe for simultaneous membrane-free neurochemical sampling and neuropharmacology in freely moving mice and rats. We will achieve this goal by pursuing the following three specific aims: (1) to develop and characterize a push-pull microsystem for membrane-free neurochemical sampling; (2) to develop a wireless, multimodal neural probe for simultaneous membrane-free neurochemical sampling and neuropharmacology; and (3) to evaluate and characterize the efficiency and functionality of the wireless, multimodal neural probe in vivo in freely moving mice and rats. The proposed research is innovative for four key reasons: First, the wireless neural probe combines the membrane-free, push-pull microsystem with a time-sequential fluid sampling device, thereby enabling the sampling of multiple neuropeptides and proteins with spatiotemporal precision. Second, the probe provides simultaneous neuropharmacology and membrane- free neurochemical sampling in awake, freely moving mice and rats, thereby making it possible to sample multiple high-molecular-weight neurochemicals and in turn guide localized pharmacological stimulation through a single platform. Third, the fully wireless, battery-free operation prevents the limitations that conventional wires and tubing connected to external hardware impose on the natural behavior of animals, thereby offering a tremendous opportunity to link neuromodulation and/or neurochemical release with natural animal behaviors related to mental disorders. Finally, the probe has lightweight construction, thereby enabling the application in small animals, such as mice, without inducing physical stress or disrupting their natural behaviors, a condition important for behavior studies related to mental disorders. The successful completion of the proposed research will yield wireless, multimodal neural probes with several innovative features for simultaneous membrane- free neurochemical sampling and neuropharmacology during freely moving behaviors. We believe that these neural probe systems will be of great interest to the neuroscience community as a way of elucidating the molecular mechanisms underlying aberrant behavior, circuit dysfunction and altered neurochemistry associated with mental disorders.