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: 10521971
• 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/10521971
• 关键词: Affect; Animal Behavior; Animals; Anxiety; Behavior; Behavioral; Benchmarking; Biosensor; Blood capillaries; Brain; Chemicals; Collection; Communities; Computer software; Detection; Development; Device Designs; Devices; Diffusion; Disease; Enzyme-Linked Immunosorbent Assay; Functional disorder; 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; Pharmacology; 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; 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; neural circuit; neurochemistry; neuroregulation; neurotechnology; new technology; operation; polypeptide; prevent; programs; prototype; relating to nervous system; 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.

项目总结/摘要 精神障碍，如抑郁症，焦虑症和许多其他疾病，影响了数百万人的生活质量 国际吧高分子量神经化学物质，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发挥着关键作用。然而，尽管开展了大量工作， 目前的测量技术，如微透析或循环伏安法，缺乏空间和时间的测量， 精确度和分子特异性来检测这些更大的分子。我们的长期目标是发展 先进的工具和方法，以了解在何处，何时，以及如何神经肽共释放调节不同的 大脑的行为输出。我们的近期目标是开发、优化、基准测试和充分验证 无线多模式神经探针，用于同时进行无膜神经化学采样， 在自由活动的小鼠和大鼠中的神经药理学。我们将通过以下三个方面来实现这一目标 具体目标：（1）开发和表征无膜神经化学的推拉微系统 采样;（2）开发无线，多模式神经探针，用于同时无膜神经化学 采样和神经药理学;和（3）评估和表征的效率和功能的 在自由活动的小鼠和大鼠体内的无线多模式神经探针。该研究具有创新性 有四个关键原因：首先，无线神经探针将无膜推拉微系统与 时间顺序流体采样装置，从而能够对多种神经肽和蛋白质进行采样 时空精确度。其次，探针同时提供神经药理学和膜- 在清醒、自由活动的小鼠和大鼠中进行自由神经化学取样，从而使取样成为可能。 多个高分子量的神经化学物质，并反过来引导局部药理刺激， 一个平台。第三，全无线、无电池操作避免了传统有线的局限性， 和连接到外部硬件的管道强加于动物的自然行为，从而提供了一种 将神经调节和/或神经化学物质释放与自然动物行为联系起来的巨大机会 与精神疾病有关。最后，探头具有轻质结构，从而使应用能够在 小动物，如老鼠，不引起身体压力或破坏其自然行为，一种条件， 对精神疾病相关的行为研究很重要成功完成拟议的研究 将产生无线，多模式神经探针与几个创新的功能，同时膜- 自由活动行为期间的自由神经化学取样和神经药理学。我们相信这些 神经探针系统作为一种阐明神经系统的方法， 异常行为、回路功能障碍和相关神经化学改变的分子机制 有精神障碍