While optogenetics is well-suited for understanding the dynamic activity of neural circuits the first central theme of the NIH BRAIN Initiative (PAR-15-090), its neurochemical impacts remain largely uncharacterized due to a lack of appropriate tools. Given that the predominant mode of cellular interactions is neurochemical, commercial development of such tools will fulfill the goals set by the first as well as the second central theme of the NIH BRAIN Initiative developing novel tools to facilitate the detailed analysis of complex circuits and provide insights into cellular interactions that underlie brain function. This R41 project aims to fulfill these goals through Aim 1 prototype development and Aim 2 prototype validation of a unified system for wireless optogenetics and brain microdialysis for small molecules (including but not limited to glutamate, dopamine, GABA, serotonin, norepinephrine and acetylcholine). Brain microdialysis is a well-established method capable of comprehensive as well as high-throughput (multiplex) neurochemical profiling. Microdialysis supports a wide range of application (neurochemical targets) as well as a high level of efficiency, sensitivity, accuracy, practicality, maintainability, and manufacturability. The proposed unified system of wireless optogenetics and brain microdialysis is expected to possess high research as well as business potentials and help address unexplored questions in neuroscience that cannot be adequately addressed by the current technologies. The prototype development (design and production) will be based on existing products from Eicom-USA. By taking advantage of our own market tested technologies, we attempt to maximize the technical feasibility, minimize the R&D challenge, and thus attain both high product development feasibility and high benefit-cost ratio (BCR) while reducing the time to market (TTM). Two systems one main and the other backup (for potential pitfalls) are proposed. The prototype validation (iterate refinement) will be achieved as specified by NIH through feedback from end-users in the context of the intended experimental use thus ensuring reliable, broad, sustainable dissemination and incorporation of the final products into regular neuroscience practice. For this premise, the prototypes will be utilized for afferent (neuronal input)-specific neurochemical profiling in freely moving animals to address an unexplored question in neuroscience. First, the expected results will validate the prototypes. Second, the results will also serve as the first direct evidence comprehensively characterizing the neurochemical impacts of optogenetics, establishing the proof of concept as well as research benefits of the proposed system, and thereby providing the marketing tools for the planned commercialization of the final product.
Public Health Relevance Statement: PROJECT NARRATIVE The purpose of this R41 project is to develop and validate the prototypes for a unified system of wireless optogenetics and brain microdialysis for small molecules, such as neurotransmitters and small peptides. The prototype will be developed (designed and produced) by taking advantage of existing technologies, and then validated through end-user feedback in the context of intended experimental use. The final product is expected to provide the means to comprehensively determine the neurochemical impacts of optogenetics that still largely remain uncharacterized due to the lack of appropriate tools and thereby satisfy the NIH Brain Initiative.
Project Terms: Acetylcholine; Address; Adopted; Amino Acids; Animals; Area; base; Biological Assay; biological systems; Biosensor; Brain; BRAIN initiative; Businesses; Cannulas; cell type; Chemicals; clinical biomarkers; commercialization; Complex; Costs and Benefits; design; Development; Dialysis procedure; Dopamine; Endocannabinoids; Engineering; Ensure; Enzymes; Evaluation; Feedback; Future; gamma-Aminobutyric Acid; Glutamates; Goals; insight; Joints; Liquid substance; manufacturing process; Marketing; Medical; Metabolic; Methods; Microdialysis; millisecond; Monitor; monoamine; Names; Nanotechnology; neural circuit; neurochemistry; Neurons; Neuropeptides; Neurosciences; Neurotransmitters; new product development; Norepinephrine; novel; Nucleic Acids; Optics; optogenetics; Peptides; Pharmaceutical Preparations; Pharmacology; Price; Process; product development; Production; prototype; Pump; Research; research and development; Resolution; Role; Sampling; Science; Serotonin; small molecule; Specific qualifier value; Specificity; Syringes; System; Techniques; Technology; temporal measurement; Testing; Time; tool; United States National Institutes of Health; usability; Validation; Wireless Technology
