Circuit Mechanisms Governing the Default Mode Network

管理默认模式网络的电路机制

• 批准号: 10576946
• 负责人: VINOD MENON
• 金额: $ 69.07万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10576946
• 关键词: Address; Alzheimer' s Disease; Anterior; Area; Attention; Attention deficit hyperactivity disorder; Attenuated; Auditory; Behavior; Behavioral; Brain; Brain Diseases; Brain region; Data; Disinhibition; Entropy; Event; Exhibits; Fiber; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Human; Image; Insula of Reil; Interneurons; Investigation; Knowledge; Link; Magnetic Resonance Imaging; Measurement; Measures; Medial; Methodology; Mus; Neurons; Output; Phase; Photometry; Prefrontal Cortex; Public Health; Repetitive Sequence; Research; Rest; Rodent; Schizophrenia; Signal Transduction; Space Models; Stimulus; Stress; Study models; System; Techniques; Time; Translational Research; Translations; autism spectrum disorder; awake; causal model; cell type; cingulate cortex; cognitive control; deviant; excitatory neuron; hemodynamics; indexing; inhibitory neuron; innovation; insight; nervous system disorder; network architecture; network dysfunction; neural circuit; neuromechanism; neurophysiology; neuropsychiatric disorder; neuropsychiatry; new technology; novel; optogenetics; prevent; response; time use

PROJECT SUMMARY Non-invasive functional magnetic resonance imaging (fMRI) has revolutionized our understanding of macroscopic functional brain networks. However, inherent constraints of current fMRI methodologies in humans limit our ability to probe the mechanisms underlying these networks. The overarching goal of this project is to shed light on cellular and circuit mechanisms underlying the functional organization of the default-mode network (DMN) – a large-scale brain network that is crucial for a wide range of behaviors. While the new technologies in rodents allows us to experimentally reveal causal control of DMN, rodent DMN topology has only been defined using resting-state fMRI, but not functionally in terms of activation or suppression of brain activity in response to behaviorally relevant salient stimuli. This represents a critical barrier preventing any straightforward translation between rodent and human DMN research findings. To address this, we developed a novel silent zero-echo- time (ZTE) fMRI technique, enabling awake rodent imaging and the use of an auditory oddball paradigm, wherein deviant oddball stimuli presented amongst a sequence of repetitive control stimuli can drive attention and suppress DMN. We also developed an MR-compatible, four-channel, spectrally-resolved fiber-photometry system, allowing concurrent recording of ground-truth neuronal activities during fMRI. To shed light on the circuit mechanisms governing the DMN, we proposed two complementary research Aims building on our rigorous prior research. In Aim 1, we will determine how attention to salient stimuli alters DMN activity and connectivity using the novel ZTE-photometry platform. In Aim 2, we will introduce time-locked optogenetics on defined cell types to causally manipulate the activity of anterior insula – the brain region assumed to be responsible for DMN dynamic switching in numerous fMRI causal modeling studies. Functionally dissecting the rodent DMN architecture is critical to the understanding of DMN transition mechanisms, which will enable us to causally model, and make predictions about brain states, bringing insight into the network basis of human behavior and neuropsychiatric/neurological disorders. 1

项目摘要 非侵入性功能磁共振成像（fMRI）彻底改变了我们的 了解宏观功能的大脑网络。 人类的方法论限制了我们探测这些网络基础的机制的能力 总体目标是阐明它们的蜂窝和电路机制 默认模式网络（DMN）的功能组织 - 一个至关重要的大型大脑网络 对于一系列行为。 DMN的因果控制，啮齿动物DMN拓扑使用状态fMRI已定义，但不 在功能上，响应于行为相关的大脑活动的激活或促进性 显着刺激。这代表了一个关键的障碍 啮齿动物和人类DMN研究结果。 时间（ZTE）fMRI技术，实现清醒的啮齿动物成像和使用听觉奇数 范式，在一系列重复对照刺激中呈现的wayin变形刺激 可以驱动Attension并抑制DMN。 光谱纤维光度法系统，允许并发地面神经元 fMRI期间的活动。 两项汇编研究的目的是在我们的严格的优先研究中构建。 对显着刺激的注意力如何使用新型的ZTE-光度法改变DMN的活性和连接 在AIM 2中，我们将在定义的细胞类型上引入时遗传学 操纵前岛的活性 - 大脑调节负责DMN动态 切换众多功能磁共振成像因果建模研究。 体系结构对于理解DMN过渡机制至关重要，这将使我们能够 因果建模，并对大脑状态做出预测，将洞察力带入网络基础 人类行为和神经精神病/神经学障碍。 1