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: 10469009
• 负责人: Kendall H. Lee
• 金额: $ 33.44万
• 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 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10469009
• 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; 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; kinetic model; 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.

项目摘要 我们建议开发和优化一种先进的神经化学记录技术 测量相对较快的生理代表性的基础浓度二到一秒的变化 特定的神经化学物质，例如多巴胺，在醒着的动物的大脑中。微透析，a 通常在体内采样技术中使用，能够衡量基础水平的变化。但是，在 练习采样时间尺度大大限于分钟到分钟的变化，遭受差 空间分辨率并诱导明显的组织损伤。同样，传统的体内电化学 记录技术（例如快速扫描的循环伏安法）本质上仅限于测量阶段 （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 拟议的电化学技术我们称为多个环状方波伏安法（M-CSWV）将启用 基础细胞外水平的神经化学物质的二对一测量 分辨率，灵敏度，特异性和最小的组织障碍。该建议利用我们独特的专业知识 在神经科学，电化学，软件开发和工程上开发和验证这部小说 神经化学记录技术用于基本神经科学研究，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并告知 我们的研究技术用于普通神经科学和医学界使用。 我们的建议试图（1）建立M-CSWV作为可靠的研究工具，能够识别和 在体内量化基础多巴胺外水平，具有无与伦比的敏感性和选择性； （2） 验证使用M-CSWV用于体内慢性选择性测量基底胺浓度和 在药物诱导的神经化学敏化的动物模型中应用。

项目成果

Mitigating the Effects of Electrode Biofouling-Induced Impedance for Improved Long-Term Electrochemical Measurements In Vivo.

• DOI: 10.1021/acs.analchem.9b05194
• 发表时间: 2020-05-05
• 期刊: Analytical chemistry
• 影响因子: 7.4
• 作者: Seaton BT;Hill DF;Cowen SL;Heien ML
• 通讯作者: Heien ML

Tonic Serotonin Measurements In Vivo Using N-Shaped Multiple Cyclic Square Wave Voltammetry.

• DOI: 10.1021/acs.analchem.1c02131
• 发表时间: 2021-12-28
• 期刊: ANALYTICAL CHEMISTRY
• 影响因子: 7.4
• 作者: Shin, Hojin;Goyal, Abhinav;Barnett, J. Hudson;Rusheen, Aaron E.;Yuen, Jason;Jha, Rohan;Hwang, Sang Mun;Kang, Yumin;Park, Cheonho;Cho, Hyun-U;Blaha, Charles D.;Bennet, Kevin E.;Oh, Yoonbae;Heien, Michael L.;Jang, Dong Pyo;Lee, Kendall H.
• 通讯作者: Lee, Kendall H.

Oxycodone-induced dopaminergic and respiratory effects are modulated by deep brain stimulation.

• DOI: 10.3389/fphar.2023.1199655
• 发表时间: 2023
• 期刊: Frontiers in pharmacology
• 影响因子: 5.6

Biocompatible reference electrodes to enhance chronic electrochemical signal fidelity in vivo.

• DOI: 10.1007/s00216-021-03640-w
• 发表时间: 2021-11
• 期刊: Analytical and bioanalytical chemistry
• 影响因子: 4.3
• 作者: Seaton BT;Heien ML
• 通讯作者: Heien ML

Feasibility of Applying Fourier Transform Electrochemical Impedance Spectroscopy in Fast Cyclic Square Wave Voltammetry for the In Vivo Measurement of Neurotransmitters.

• DOI: 10.1021/acs.analchem.1c02308
• 发表时间: 2021-12-07
• 期刊: ANALYTICAL CHEMISTRY
• 影响因子: 7.4
• 作者: Park, Cheonho;Hwang, Sangmun;Kang, Yumin;Sim, Jeongeun;Cho, Hyun U.;Oh, Yoonbae;Shin, Hojin;Kim, Do Hyoung;Blaha, Charles D.;Bennet, Kevin E.;Lee, Kendall H.;Jang, Dong Pyo
• 通讯作者: Jang, Dong Pyo