Mechanisms underlying positive and negative BOLD in the striatum

纹状体中正负 BOLD 的潜在机制

• 批准号: 9922502
• 负责人: Yen-Yu Ian Shih
• 金额: $ 10万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-09 至 2022-08-22
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9922502
• 关键词: Acetylcholine; Address; Area; BRAIN initiative; Blood; Blood Vessels; Brain; Brain region; Calcium Signaling; Cell physiology; Cerebrovascular Circulation; Cognition; Corpus striatum structure; Coupled; Coupling; DRD2 gene; Data; Data Analyses; Dopamine; Dopamine Receptor; Dynorphins; Electrophysiology (science); Fiber; Foundations; Functional Magnetic Resonance Imaging; Funding; Human; Interneurons; Knowledge; Major Depressive Disorder; Measurement; Measures; Medial; Mediating; Modality; Molecular; Motivation; Muscarinics; Neurons; Neurosciences; Neurotransmitters; Obsessive-Compulsive Disorder; Parkinson Disease; Parvalbumins; Pathway interactions; Peptides; Periodicity; Pharmacology; Photometry; Play; Positioning Attribute; Process; Rattus; Research; Rewards; Role; Scanning; Schizophrenia; Sensorimotor functions; Signal Transduction; Somatostatin; Techniques; Technology; Testing; Transgenic Organisms; addiction; base; blood oxygen level dependent; blood oxygenation level dependent response; cell type; cholinergic; hemodynamics; insight; kappa opioid receptors; multimodality; nervous system disorder; neuropeptide Y; neuropsychiatric disorder; neurotransmission; neurovascular coupling; novel; optical fiber; optogenetics; postsynaptic; receptor; relating to nervous system; response; tool

PROJECT SUMMARY Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) is widely used as a non-invasive technique to study brain function. It operates based on the premise that cerebral blood flow renews the supply of energetic substrates to brain regions with increased neuronal activity in a process known as neurovascular coupling. Accumulating results from our group and others indicate that conventional neurovascular coupling may not apply to the striatum and is likely that atypical vasoactive neurotransmission has been playing a largely unaccounted role in this brain area. The striatum is a critical hub for cognition, motivation, reward, and sensorimotor function, and understanding its aberrant hemodynamic activity will provide crucial context to these fields of research. We have developed two central hypotheses: that positive BOLD in the striatum is mediated through dopamine release but not local neuronal activity, and that negative BOLD in the striatum is induced by local neuronal activation and mediated through their downstream vasoconstrictive neurotransmission. We will use 3 neural modulation approaches, including optogenetics, chemogenetics, and pharmacology, together with 4 recording technologies, including fMRI, electrophysiology, fast-scan cyclic voltammetry, and optical fiber-photometry to manipulate and acquire the changes in BOLD, dopamine release, and neuronal activity in the striatum. We expect our results to provide novel insights into BOLD mechanisms, and lay the foundation for accurate fMRI data interpretation in subcortical brain areas that do not obey the traditional neurovascular coupling rules. 1

项目摘要 血氧水平依赖性功能磁共振成像（BOLD fMRI）是目前广泛应用的一种功能磁共振成像技术 作为研究大脑功能的非侵入性技术。它的原理是脑血流量 在一个已知的过程中， 神经血管耦合。我们小组和其他人的累积结果表明， 神经血管偶联可能不适用于纹状体， 在这个大脑区域中扮演着一个很大的角色。纹状体是认知的关键中枢， 动机，奖励和感觉运动功能，并了解其异常血流动力学活动将提供 这些研究领域的重要背景。我们提出了两个中心假设： 纹状体是通过多巴胺释放而不是局部神经元活动来介导， 纹状体是由局部神经元激活诱导的，并通过其下游血管收缩介导。 神经传递我们将使用3种神经调节方法，包括光遗传学，化学遗传学， 药理学，连同4个记录技术，包括功能磁共振成像，电生理学，快速扫描循环 伏安法和光纤光度法来操纵和获取BOLD，多巴胺释放， 和纹状体的神经元活动。我们希望我们的研究结果能为BOLD机制提供新的见解， 并为在不服从大脑皮层的皮层下区域进行精确的功能磁共振成像数据解释奠定了基础。 传统的神经血管耦合规则。 1