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

用于同步无膜神经化学采样和神经药理学的无线多模态神经探针

• 批准号: 10646362
• 负责人: Yi Zhang
• 金额: $ 49.17万
• 依托单位: UNIVERSITY OF CONNECTICUT STORRS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-15 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10646362
• 关键词: Affect; Animal Behavior; Animals; Anxiety; Behavior; Behavioral; Benchmarking; Biosensor; Blood capillaries; Brain; Cell Membrane Permeability; Chemicals; Collection; Color; Communities; Computer software; Detection; Development; Device Designs; Devices; Diffusion; Disease; Enzyme-Linked Immunosorbent Assay; Functional disorder; Genetic; Goals; Human; Knowledge; Lateral Hypothalamic Area; Link; Liquid Chromatography; Liquid substance; Measurement; Membrane; Mental Depression; Mental disorders; Methods; Microdialysis; Modeling; Molecular; Molecular Weight; Monitor; Mus; Neurons; Neuropeptides; Neuropharmacology; Neurosciences; Outcome; Output; Oxidation-Reduction; Periodicity; Persons; Play; Power Sources; Process; Proteins; Psyche structure; Public Health; Quality of life; Rattus; Research; Resolution; Role; Sampling; Scanning; Silicon Dioxide; Specificity; Stress; System; Technology; Time; Tube; Work; absorption; awake; behavioral study; carbon fiber; cell type; design; gamma-Aminobutyric Acid; in vivo; innovation; interest; light weight; liquid chromatography mass spectrometry; microsystems; miniaturize; multidisciplinary; multimodality; nano; neural; neural circuit; neurochemistry; neuroregulation; neurotechnology; new technology; operation; pharmacologic; polypeptide; prevent; prototype; sensor; sensor technology; small molecule; spatiotemporal; specific biomarkers; tandem mass spectrometry; technology validation; tool; wireless; wireless electronic; wireless implant

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.

项目摘要/摘要 抑郁症，焦虑和许多其他人的精神障碍会影响数百万人的生活质量 全世界。高分子体重神经化学物质，例如神经肽和其他多肽 神经化学物质，在这些精神障碍的各个方面起关键作用。但是，尽管工作很大 当前的测量技术，例如微透析或环状伏安法，缺乏空间和时间 精度和分子特异性检测这些较大的分子。我们的长期目标是发展 高级工具和方法，以了解何时，何时以及如何调节神经肽的何时，如何调节多样化 大脑的行为输出。我们的直接目标是开发，优化，基准和完全验证 无线，多模式神经探针，用于同时无膜神经化学采样和 自由移动的小鼠和大鼠的神经药理学。我们将通过追求以下三个来实现这一目标 具体目的：（1）开发和表征无膜神经化学的推扣微系统 采样; （2）开发一种无线的多模式神经探针，以同时无膜神经化学 抽样和神经药理学； （3）评估和表征 自由移动的小鼠和大鼠的无线，多模式的神经探针。拟议的研究是创新的 出于四个关键原因：首先，无线神经探针将无膜的，推杆微系统与 时间序列的流体采样装置，从而实现了多种神经肽和蛋白质的采样 具有时空精度。其次，探针提供同时的神经药理学和膜 - 在清醒，自由移动的小鼠和大鼠中进行免费神经化学采样，从而可以采样 多种高分子量神经化学物质，进而指导局部药理刺激 一个平台。第三，完全无线的无电池操作阻止了常规电线的局限性 与外部硬件相连的管道对动物的自然行为施加了 将神经调节和/或神经化学释放与自然动物行为联系起来的巨大机会 与精神障碍有关。最后，该探针具有轻巧的结构，从而使应用程序能够 小动物，例如小鼠，没有诱导身体压力或破坏其自然行为，条件 对于与精神障碍有关的行为研究很重要。拟议研究的成功完成 将产生无线的多模式神经探针，并具有几种创新特征，可同时使用膜 自由移动行为期间的自由神经化学采样和神经药理。我们相信这些 神经科学社区将引起神经探测系统的极大兴趣，以阐明 分子机制的基本异常行为，电路功能障碍和神经化学改变相关的分子机制 患有精神障碍。