Fast Online Microdialysis/Liquid Chromatography for Monoamine Neurotransmitters

单胺神经递质的快速在线微透析/液相色谱

• 批准号: 9091642
• 负责人: STEPHEN G. WEBER
• 金额: $ 32.01万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-15 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9091642
• 关键词: Address; Adopted; Alcohol abuse; Animal Disease Models; Animals; Antidepressive Agents; Anxiety; Behavior; Brain; Brain Injuries; Chemicals; Collaborations; Corpus striatum structure; Coupled; Cues; Detection; Diagnostic; Dopamine; Drug abuse; Event; Fluoxetine; Functional disorder; Future; Goals; Health; High temperature of physical object; Human; In Vitro; Investigation; Liquid Chromatography; Measurement; Measures; Mental Depression; Methods; Microdialysis; Migraine; Neurotransmitters; Patients; Plant Roots; Rattus; Reporting; Research Personnel; Resolution; Rewards; Role; Sampling; Scanning; Scheme; Scientist; Serotonin; Signal Transduction; Speed; Stress; System; Techniques; Temperature; Therapeutic; Time; Trauma; Work; anxiety-related behavior; base; brain tissue; classical conditioning; empowered; extracellular; feeding; improved; in vivo; insight; instrument; monoamine; nanomolar; neurochemistry; neurotransmission; pressure; research study; sound; spreading depression; temporal measurement; transmission process

DESCRIPTION (provided by applicant): Microdialysis provides a window on the brain. It permits measurements to be made of the extracellular concentration of chemicals whose primary role is an extracellular function, for example neurotransmitters. It has been widely adopted for investigations in animal models of disease and trauma and indeed in humans suffering trauma. The technique, as powerful as it is, has one major limitation - it cannot measure rapid changes that are relevant to phenomena such as spreading depolarization and behavior. There is a large gap in the time regime over which scientists can measure extracellular concentrations of the neurotransmitters dopamine (few nanomolar basal levels) and serotonin (sub-nanomolar basal levels) in the sub-minute to five minute range. A complementary technique, fast scan cyclic voltammetry measures changes in concentrations over the sub-second to several second timeframe. Based on our sound theoretical insight and technical improvements, we propose to improve the timescale of microdialysis to cover this important range. We will address three types of experiments with the new capability. (1) Are serotonin oscillations we have seen in preliminary work due to spreading depolarization? (2) What changes in the stress/anxiety-related neurotransmitter serotonin (5-hydroxytryptamine) are seen during the time an animal is making a decision in a stressful situation? (3) Can microdialysis be used to distinguish dopamine release upon an animal's receiving a reward from dopamine release upon the animal's receiving a cue associated with the reward?

描述（由申请人提供）：微透析为大脑提供了一个窗口。它允许测量其主要作用是细胞外功能的化学物质（例如神经递质）的细胞外浓度。它已被广泛用于研究疾病和创伤的动物模型，甚至在人类遭受创伤。这项技术虽然强大，但有一个主要的局限性-它不能测量与扩散去极化和行为等现象相关的快速变化。科学家可以在亚分钟到五分钟的范围内测量神经递质多巴胺（几纳摩尔基础水平）和血清素（亚纳摩尔基础水平）的细胞外浓度的时间制度存在很大的差距。作为一种补充技术，快速扫描循环伏安法可以在亚秒到几秒的时间范围内测量浓度的变化。基于我们良好的理论洞察力和技术改进，我们建议提高微透析的时间尺度，以覆盖这一重要范围。我们将讨论三种类型的实验与新的能力。(1)我们在初步工作中看到的血清素振荡是否是由于扩散去极化造成的？(2)在动物在紧张的情况下做出决定的过程中，与压力/焦虑相关的神经递质血清素（5-羟色胺）发生了什么变化？(3)微透析能否用于区分动物接受奖励时的多巴胺释放和动物接受与奖励相关的提示时的多巴胺释放？