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

基本信息

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
项目类别：
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

项目摘要

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）：微透析提供了大脑的窗口。它允许测量化学物质的细胞外浓度，其主要作用是细胞外功能，例如神经递质。它已被广泛用于疾病和创伤动物模型以及实际上人类创伤的调查。该技术功能强大，它具有一个主要限制 - 它无法衡量与现象相关的快速变化，例如扩散去极化和行为。时间机制存在很大的差距，科学家可以测量神经递质多巴胺的细胞外浓度（少量纳摩尔基水平）和5-羟色胺（亚纳米摩尔基底水平）在五分钟至五分钟范围内。互补的技术，快速扫描循环伏安法测量浓度的浓度变化在第秒至几个时间范围内。根据我们的合理理论洞察力和技术改进，我们建议改善微透析的时间范围，以涵盖这一重要范围。我们将通过新功能讨论三种类型的实验。（1）由于扩散去极化，我们在初步工作中看到的5-羟色胺振荡吗？（2）在动物在压力良好的情况下做出决定的时候，与压力/焦虑相关的神经递质5-羟色胺（5-羟色胺）发生了什么变化？（3）微透析可用于区分动物在动物获得与奖励相关的提示时从多巴胺释放中获得奖励后的多巴胺释放吗？