Development of an innovative in vivo voltammetric technique for measurements of tonic serotonin concentrations in the mammalian brain.

开发一种创新的体内伏安技术，用于测量哺乳动物大脑中的补给血清素浓度。

• 批准号: 10559303
• 负责人: Kendall H. Lee
• 金额: $ 59.14万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2027-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10559303
• 关键词: Acute; Address; Adopted; Adsorption; Anesthesia procedures; Animals; Area; Behavior; Behavioral; Biochemical; Brain; Brain region; Chemicals; Chronic; Clinical; Communities; Development; Dialysis procedure; Dimensions; Disease; Electric Capacitance; Electrochemistry; Electrodes; Engineering; Equilibrium; Fourier Transform; Future; Hippocampus; Image; Lead; Link; Longevity; Measurement; Measures; Medical; Mental Depression; Mental disorders; Methods; Microdialysis; Microelectrodes; Modeling; Monitor; Neurons; Neurosciences; Neurosciences Research; Oxidation-Reduction; Pathology; Performance; Periodicity; Phase; Physiological; Physiology; Process; Proteins; Protocols documentation; Publications; Publishing; Rattus; Reaction; Research; Resistance; Resolution; Sampling; Scanning; Serotonin; Shapes; Signal Transduction; Specificity; Spectrum Analysis; Standardization; Stimulus; Substantia nigra structure; Surface; System; Techniques; Technology; Testing; Time; Tissues; Validation; Variant; awake; carbon fiber; dorsal raphe nucleus; electric impedance; extracellular; implantation; in vivo; in vivo monitoring; innovation; meter; nervous system disorder; neurochemistry; neurophysiology; neuropsychiatric disorder; neuroregulation; neurotransmission; novel; novel therapeutics; pharmacologic; sensor; software development; surface coating; temporal measurement; tool; transmission process

PROJECT SUMMARY We propose to develop and optimize an advanced neurochemical recording technique that would be able to measure relatively rapid physiologically representative second-to-second changes in tonic concentrations of specific neurochemicals, such as serotonin, in the brains of awake behaving animals. Microdialysis, a commonly used in vivo sampling technique, is able to measure changes that occur in tonic levels. However, in practice the sampling timescale is significantly limited to minute-to-minute changes and it suffers from poor spatial resolution and induces significant tissue damage. Present voltammetry technique can provide tonic measurement capability. However, it raises concerns for accurate quantification due to the limited approach to eliminate background capacitive current. Furthermore, limited biofouling has been shown, limiting its use for long-term tonic serotonin measurements in awake behaving animals. The proposed electrochemical technique we call N-shaped Multiple Cyclic Square Wave Voltammetry (N-MCSWV) will enable second-to-second measurements of tonic extracellular levels of serotonin with exceptional spatial resolution, sensitivity, specificity, selectivity, and diminished biofouling. This proposal leverages our unique expertise in neuroscience, electrochemistry, software development, and engineering to develop and validate this novel neurochemical recording technology for broad use in basic neuroscience research, clinical brain neuromodulation, and a variety of electrochemical applications. Our initial animal studies will guide and inform the application of our investigational technique for use by the general neuroscience and medical community. Our proposal seeks to (1) establish N-MCSWV as a reliable research tool that is capable of identifying and quantifying tonic serotonin extracellular levels in vivo with unsurpassed sensitivity, selectivity, and minimize biofouling, (2) apply Fourier transform electrochemical impedance spectroscopy to N-MCSWV to monitor the degree of electrode biofouling in vivo, and (3) validate the use of N-MCSWV for in vivo, acutely and chronically, selective measurement of tonic serotonin concentrations.

项目概要 我们建议开发和优化先进的神经化学记录技术，该技术能够 测量相对快速的生理代表性的补给浓度的每秒变化 清醒行为动物大脑中的特定神经化学物质，例如血清素。微透析，一种 常用的体内采样技术能够测量紧张水平发生的变化。然而，在 实践中，采样时间尺度明显限于每分钟的变化，并且它的性能较差 空间分辨率并引起显着的组织损伤。目前的伏安技术可以提供补品 测量能力。然而，由于方法有限，它引起了人们对准确量化的担忧。 消除背景电容电流。此外，已显示出有限的生物污垢，限制了其在 对清醒行为动物进行长期的强直血清素测量。所提出的电化学技术 我们称之为 N 形多重循环方波伏安法 (N-MCSWV) 将实现秒到秒 具有卓越的空间分辨率、灵敏度、 特异性、选择性和减少生物污垢。该提案利用了我们独特的专业知识 神经科学、电化学、软件开发和工程来开发和验证这部小说 神经化学记录技术广泛应用于基础神经科学研究、临床大脑 神经调节和各种电化学应用。我们最初的动物研究将指导和告知 我们的研究技术的应用，供一般神经科学和医学界使用。 我们的建议旨在 (1) 将 N-MCSWV 建立为可靠的研究工具，能够识别和 以无与伦比的灵敏度、选择性和最小化体内定量血清素细胞外水平 生物污垢，（2）将傅里叶变换电化学阻抗谱应用于N-MCSWV来监测 体内电极生物污染程度，以及 (3) 验证 N-MCSWV 在体内急性和长期的使用， 选择性测量补品血清素浓度。