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.

项目概要/摘要 抑郁、焦虑等精神障碍影响着数百万人的生活质量 全世界。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，尽管工作强度很大， 当前的测量技术，例如微透析或循环伏安法，缺乏空间和时间 检测这些较大分子的精度和分子特异性。我们的长期目标是发展 先进的工具和方法来了解神经肽共释放在何处、何时以及如何调节不同的 大脑的行为输出。我们的近期目标是开发、优化、基准测试并充分验证 无线、多模式神经探针，用于同时无膜神经化学采样和 自由活动的小鼠和大鼠的神经药理学。我们将通过以下三点努力实现这一目标 具体目标：（1）开发和表征无膜神经化学物质的推拉微系统 采样; (2) 开发无线、多模态神经探针，用于同步无膜神经化学物质 采样和神经药理学； (3) 评估和表征系统的效率和功能 自由移动的小鼠和大鼠体内的无线多模式神经探针。所提出的研究具有创新性 有四个关键原因：首先，无线神经探针将无膜推拉式微系统与 时序流体采样装置，从而能够对多种神经肽和蛋白质进行采样 具有时空精度。其次，该探针同时提供神经药理学和膜- 对清醒、自由活动的小鼠和大鼠进行免费神经化学采样，从而使采样成为可能 多种高分子量神经化学物质，进而通过引导局部药理刺激 单一平台。第三，完全无线、无电池的操作避免了传统有线的限制 连接到外部硬件的管道会影响动物的自然行为，从而提供 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 与精神障碍有关。最后，该探头具有轻质结构，从而能够在 小动物，例如老鼠，不会引起身体压力或破坏其自然行为，这是一种情况 对于与精神障碍相关的行为研究很重要。顺利完成拟议的研究 将产生无线、多模式神经探针，具有多种创新功能，可同时进行膜- 自由移动行为期间的自由神经化学采样和神经药理学。我们相信，这些 神经探针系统将引起神经科学界的极大兴趣，作为阐明神经科学的一种方式。 异常行为、回路功能障碍和相关神经化学改变的分子机制 患有精神障碍。