Simultaneous optical voltage imaging and fMRI in behaving mice

对行为小鼠进行同步光电压成像和功能磁共振成像

• 批准号: 10608058
• 负责人: Patrick Doran
• 金额: $ 3.91万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10608058
• 关键词: Address; Animal Model; Animals; Anterior; Area; Behavioral; Biological; Blood; Blood Vessels; Blood flow; Brain; Brain imaging; Calcium; Cerebral cortex; Cerebrovascular Circulation; Cerebrovascular system; Communication; Complex; Conscious; Data; Dependence; Development; Devices; Emotions; Engineering; Foundations; Functional Imaging; Functional Magnetic Resonance Imaging; Future; Generations; Goals; Head; Hemoglobin; Human; Image; Imaging technology; Knowledge; Lateral; Learning; Magnetic Resonance Imaging; Magnetism; Measurement; Medical Research; Microscopic; Mind; Molecular; Monitor; Motor Cortex; Mus; Neurons; Neurosciences; Optics; Oxygen; Pathway interactions; Pharmacology; Physiological; Population; Process; Property; Protocols documentation; Publications; Research Personnel; Rest; Role; Side; Signal Transduction; Signaling Molecule; Somatosensory Cortex; Stimulus; Techniques; Technology; Translating; Vasodilation; Water; awake; blood oxygen level dependent; blood oxygenation level dependent imaging; blood oxygenation level dependent response; brain research; career; cell type; constriction; contrast imaging; diagnostic tool; experimental study; hemodynamics; in vivo; inhibitory neuron; insight; interest; knowledge base; magnetic field; neural; neuropeptide Y; non-invasive imaging; optical imager; optical imaging; optogenetics; receptor; response; sensor; tool; two-photon; vasoconstriction; voltage

Abstract Among the various areas in brain research, brain imaging is the most appreciated by a general audience. Due to recent advances in imaging technologies, we can “see” brain in action. One of the most promising and widely used noninvasive imaging technologies is functional Magnetic Resonance Imaging (fMRI) based on the Blood Oxygenation Level Dependent (BOLD) contrast. However, the physiological basis of this technique is still poorly understood. Electrical recordings and in vivo 2-photon calcium imaging have enabled us to understand functions of identified neuronal populations. A major challenge of today is to connect these microscopic neuroscience insights, which require invasive imaging and recording tools, with macroscopic noninvasive fMRI signals. To address this challenge, I propose to combine optical imaging of electrical neuronal activity simultaneously with BOLD fMRI measurements in awake behaving mice. These experiments will leverage an MRI-compatible optical imager that I have engineered and integrated into an animal holder since the first submission (the old Aim 1). In the new Aim 1, I will explore the relationship of cell-type-specific neuronal voltage and BOLD fMRI signals during spontaneous and task-induced neuronal activity. The BOLD signal can be both positive and negative, and previous findings from my lab demonstrate the importance of a specific population of cortical inhibitory neurons that release a signaling molecule Neuropeptide Y (NPY) causing vasoconstriction via Y1 receptors. In the new Aim 2, I will address the role of NPY-positive neurons in generation of BOLD signals. To this end, I will combine voltage imaging and BOLD fMRI with optogenetic silencing of NPY-positive neurons and antagonizing the NPY-Y1 pathway. From a technological perspective, my study will be the first to perform voltage imaging inside an MRI scanner. On the biological side, my study will provide empirical data addressing the relationship between cell-type- specific neuronal activity and the BOLD signal and evaluate the dependence of a specific macroscopic imaging signal – negative BOLD – on a concrete cellular/molecular pathway. While working on my dissertation project, I will expand my scientific knowledge base, produce high-profile publications, and build a foundation for my future career as an independent investigator.

抽象的 在脑研究的各个领域中，脑成像是最受大众欢迎的。 随着成像技术的最新进展，我们可以“看到”大脑的运作，这是最有前途和最有效的技术之一。 广泛使用的无创成像技术是基于功能磁共振成像（fMRI） 然而，血氧水平相关（BOLD）对比是该技术的生理基础。 电记录和体内 2 光子钙成像使我们能够了解这一点。 当今的一个主要挑战是将这些神经元群体联系起来。 微观神经科学见解，需要侵入性成像和记录工具，以及宏观 无创功能磁共振成像信号。 为了应对这一挑战，我建议将电神经活动的光学成像结合起来 同时对清醒行为的小鼠进行大胆的功能磁共振成像测量，这些实验将利用这些实验。 一个与 MRI 兼容的光学成像仪，我从第一台起就设计并集成到动物支架中 提交（旧目标 1） 在新目标 1 中，我将探讨细胞类型特异性神经的关系。 自发和任务诱导的神经活动期间的电压和 BOLD fMRI 信号 BOLD 信号可以。 既是积极的又是消极的，我的实验室之前的发现证明了特定的重要性 释放信号分子神经肽 Y (NPY) 的皮质抑制性神经元群 在新目标 2 中，我将讨论 NPY 阳性神经元在血管收缩中的作用。 为此，我将电压成像和 BOLD fMRI 与光遗传学结合起来。 沉默 NPY 阳性神经元并拮抗 NPY-Y1 通路。 从技术角度来看，我的研究将是第一个在 MRI 扫描仪内进行电压成像的研究。 在生物学方面，我的研究将提供解决细胞类型之间关系的经验数据 特定神经元活动和 BOLD 信号并评估特定宏观成像的依赖性 信号 - 负粗体 - 在具体的细胞/分子途径上，我在从事我的论文项目时。 将扩大我的科学知识基础，出版备受瞩目的出版物，并为我的未来奠定基础 未来的职业生涯是作为一名独立调查员。