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

项目摘要 血氧水平依赖性功能磁共振成像（BOLD fMRI）是一种非侵入性的 一种通过局部氧合增加来推断大脑活动增加的成像技术 血红蛋白。解释BOLD数据很大程度上取决于神经元放电和血液增加的假设。 在一个被称为神经血管耦合的过程中，大脑中的血流直接相关。然而， 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视了， 目前的解释是不完整的。这对于理解纹状体（一个大脑区域）尤其重要 在奖励预测和药物成瘾中，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是丰富的，但它对纹状体的调节作用， 血流动力学知之甚少。这项拟议的工作旨在了解多巴胺和纹状体 神经元有助于对直接脑刺激的正向和负向BOLD响应。 通过使用一套尖端技术，我们将选择性地刺激多巴胺神经元或纹状体神经元 与光遗传学和系统地消除神经元或神经递质受体成分， 它们对血液动力学反应的贡献。响应于刺激，快速扫描循环伏安法将 在植入式微电极上检测局部多巴胺和氧气的变化，并使用功能磁共振成像 同时监测大脑中氧气的变化。药理学和化学遗传学将用于 选择性地激活或抑制受体和细胞类型。这些实验将扩展我们解读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， 血流动力学反应。

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.