Development of advanced voltammetric method for basal neurotransmitter level measurement

开发用于基础神经递质水平测量的先进伏安法

• 批准号: 9796267
• 负责人: Charles Blaha
• 金额: $ 34.92万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9796267
• 关键词: Acute; Adsorption; Advanced Development; Amphetamines; Animal Model; Animals; Behavior; Behavioral; Biological; Brain; Cells; Characteristics; Chemicals; Chronic; Clinical; Communities; Computer software; Corpus striatum structure; Data; Data Analyses; Dialysis procedure; Dimensions; Disease; Dopamine; Dopaminergic Agents; Drug Modelings; Electrochemistry; Engineering; Equilibrium; Future; Goals; Implant; In Vitro; Injections; Investigation; Kinetics; Lead; Link; Literature; Measurement; Measures; Medical; Mental disorders; Methods; Microdialysis; Microelectrodes; Modeling; Neurons; Neurosciences; Neurosciences Research; Neurotransmitters; Periodicity; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Phase; Physiological; Principal Component Analysis; Process; Publishing; Rattus; Research; Resolution; Sampling; Scanning; Sensitivity and Specificity; Slice; Spectrum Analysis; Standardization; Stimulus; Surface; Synapses; Synaptic plasticity; System; Techniques; Technology; Testing; Time; Tissues; Validation; Variant; awake; base; behavioral sensitization; carbon fiber; electric impedance; extracellular; in vivo; method development; nervous system disorder; neurochemistry; neuropsychiatric disorder; neuroregulation; neurotransmission; noradrenergic; novel; phase change; receptor; response; software development; temporal measurement; tool; two-dimensional

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 basal concentrations of specific neurochemicals, such as dopamine, in the brains of awake behaving animals. Microdialysis, a commonly used in vivo sampling technique, is able to measure changes that occur in basal 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. As well, conventional in vivo electrochemical recording techniques, such as fast-scan cyclic voltammetry, are intrinsically limited to measuring phasic (stimulation-induced) changes in neurochemical concentrations and not changes in basal concentrations. The proposed electrochemical technique we call Multiple Cyclic Square Wave Voltammetry (M-CSWV) will enable second-to-second measurements of basal extracellular levels of neurochemicals with exceptional spatial resolution, sensitivity, specificity, and minimal tissue disturbance. 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 M-CSWV as a reliable research tool that is capable of identifying and quantifying basal dopamine extracellular levels in vivo with unsurpassed sensitivity and selectivity; and (2) validate the use of M-CSWV for in vivo chronic selective measurement of basal dopamine concentrations and application in an animal model of drug-induced neurochemical sensitization.

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基础浓度的每秒变化 清醒行为动物大脑中的特定神经化学物质，例如多巴胺。微透析，一种 常用的体内采样技术，能够测量基础水平发生的变化。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。同样，传统的体内电化学 记录技术，例如快速扫描循环伏安法，本质上仅限于测量相 （刺激引起的）神经化学浓度的变化而不是基础浓度的变化。这 提出的电化学技术，我们称为多循环方波伏安法（M-CSWV）将能够实现 神经化学物质的基础细胞外水平的每秒测量具有特殊的空间 分辨率、灵敏度、特异性和最小的组织干扰。该提案利用了我们独特的专业知识 神经科学、电化学、软件开发和工程领域的人员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 M-CSWV 建立为可靠的研究工具，能够识别和 以无与伦比的灵敏度和选择性定量体内基础多巴胺细胞外水平；和（2） 验证 M-CSWV 在体内长期选择性测量基础多巴胺浓度的用途，以及 在药物诱导的神经化学致敏动物模型中的应用。