Administrative Supplement: Neuronal and Dopaminergic Contributions to Dissimilar Evoked Hemodynamic Responses in the Striatum

行政补充：神经元和多巴胺能对纹状体不同诱发血流动力学反应的贡献

• 批准号: 10299755
• 负责人: Lindsay Walton
• 金额: $ 3.52万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-01 至 2021-08-23
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10299755
• 关键词: Acute; Administrative Supplement; Affect; Agonist; Attention Deficit Disorder; Automobile Driving; Behavior; Blood Vessels; Blood flow; Brain; Brain region; Caliber; Cells; Chemicals; Cognition; Corpus striatum structure; Coupled; Coupling; DRD2 gene; Data; Dopamine; Dopamine Receptor; Dorsal; Drug Addiction; Functional Magnetic Resonance Imaging; Hemoglobin; Imaging Techniques; Injections; Location; Long-Evans Rats; Measures; Mediating; Methods; Microelectrodes; Mind; Monitor; Motor Cortex; Neurons; Neurotransmitter Receptor; Neurotransmitters; Oxygen; Parkinson Disease; Pathology; Pathway interactions; Periodicity; Pharmaceutical Preparations; Pharmacology; Play; Process; Rattus; Receptor Activation; Receptor Cell; Research; Resolution; Rewards; Role; Scanning; Signal Transduction; Stimulus; Substantia nigra structure; Synapses; Techniques; Testing; Vasodilation; Virus; Work; blood oxygen level dependent; butyrolactone; cell type; cohort; designer receptors exclusively activated by designer drugs; dopaminergic neuron; experimental study; hemodynamics; imaging study; light gated; millisecond; neuroimaging; neurological pathology; neurotransmission; neurovascular coupling; non-invasive imaging; optogenetics; pars compacta; prevent; receptor; response; vasoconstriction

PROJECT SUMMARY Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) is a non-invasive imaging technique that infers the presence of increased brain activity from localized increases in oxygenated hemoglobin. Interpreting BOLD data largely depends on the assumption that neuronal firing and increased blood flow directly correlate across the brain in a process known as neurovascular coupling. However, the influence of vasoactive neurotransmitters on BOLD signals have been largely ignored in interpreting brain functionality, such that current interpretations are incomplete. This is especially crucial to understand in the striatum, a brain region heavily involved in reward prediction and drug addiction, where coupling is not conserved. The vasoactive neurotransmitter dopamine is abundant throughout the striatum, yet its modulatory role over striatal hemodynamics is poorly understood. This proposed work seeks to understand how dopamine and striatal neurons contribute to both positive and negative BOLD responses to direct brain stimulation. By using a cutting-edge suite of techniques, we will selectively stimulate dopamine neurons or striatal neurons with optogenetics and systematically eliminate neuronal or neurotransmitter receptor components to investigate their contribution to the hemodynamic response. In response to a stimulus, fast-scan cyclic voltammetry will detect local dopamine and oxygen changes at an implantable microelectrode, and fMRI will be used simultaneously to monitor oxygen changes across the brain. Pharmacology and chemogenetics will be used to selectively activate or inhibit receptors and cell types. These experiments will expand our ability to interpret fMRI data accurately by establishing and quantifying both neuronal and neurotransmitter contributions to the striatal hemodynamic response.

项目总结 血氧水平依赖的功能磁共振成像(BOLD FMRI)是一种无创的 一种成像技术，从局部的含氧量增加推断大脑活动增加的存在 血红蛋白。对大胆数据的解释在很大程度上取决于神经元放电和血液增加这一假设 在被称为神经血管耦合的过程中，血流在大脑中直接相关。然而，中国的影响力 在解释大脑功能时，BOLD信号上的血管活性神经递质在很大程度上被忽略了，例如 目前的解释是不完整的。这对于理解纹状体这一大脑区域尤为关键。 严重参与奖赏预测和吸毒成瘾，这些方面的耦合是不保守的。血管活性 神经递质多巴胺在整个纹状体中都很丰富，但它对纹状体的调节作用 人们对血液动力学知之甚少。这项拟议的工作试图了解多巴胺和纹状体 对于直接的大脑刺激，神经元对积极和消极的大胆反应都有贡献。 通过使用一套尖端技术，我们将有选择地刺激多巴胺神经元或纹状体神经元 用光遗传学和系统消除神经元或神经递质受体成分来研究 它们对血流动力学反应的贡献。响应于刺激，快速扫描循环伏安法将 在可植入的微电极上检测局部多巴胺和氧气的变化，将使用功能磁共振 同时监测整个大脑的氧气变化。药理学和化学遗传学将被用于 选择性地激活或抑制受体和细胞类型。这些实验将扩大我们解释功能磁共振成像的能力 通过建立和量化神经元和神经递质对纹状体的贡献来准确地获得数据 血流动力学反应。