Combing resting state functional magnetic resonance imaging with chemogenetic modulation to characterize connectivity of the Salience Network

将静息态功能磁共振成像与化学遗传学调制相结合来表征显着网络的连接性

• 批准号: 10584561
• 负责人: Adriana kelly-Ann Cushnie
• 金额: $ 2.18万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-05 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10584561
• 关键词: Acute; Agonist; Amygdaloid structure; Anatomy; Anterior; Anxiety Disorders; Attention; Award; Axon; Binding; Biological; Brain; Brain Diseases; Brain region; Cells; Clozapine; Cognitive; Communication; Complex; Cues; Data Analyses; Decision Making; Detection; Diagnosis; Disease; Doctor of Philosophy; Dose; Drug Receptors; Emotional; Endowment; Etiology; Experimental Designs; Faculty; Functional Magnetic Resonance Imaging; Future; G-Protein-Coupled Receptors; Genetic; Genetic Induction; Genetic Techniques; Goals; Human; Injections; Learning; Ligand Binding; Ligands; Link; MRI Scans; Major Depressive Disorder; Manuscripts; Measures; Mediating; Mental disorders; Neurons; Oral; Oxides; Penetrance; Pharmaceutical Preparations; Population; Positioning Attribute; Regional Anatomy; Research; Resources; Rest; Rodent; Scanning; Schizophrenia; Sensory; Signal Transduction; Statistical Data Interpretation; Stimulus; Techniques; Technology; Thalamic structure; Time; Training; Universities; Ventral Striatum; Ventral Tegmental Area; Viral; Viral Vector; Work; Writing; autism spectrum disorder; blood oxygen level dependent; career; cingulate cortex; computer program; design; designer receptors exclusively activated by designer drugs; experimental study; hemodynamics; in vivo; insight; network dysfunction; neural; neuroimaging; neuropsychiatric disorder; nonhuman primate; novel; novel strategies; receptor; skills; specific biomarkers

Project Summary We are constantly confronted with numerous stimuli that compete for limited neural resources. A salient cue is one that is important and noticeable. The Salience Network (SN), a set of brain regions that are consistently co-activated across different conditions and at rest, is involved in the detection of attention-commanding external and internal stimuli for properly allocating cognitive resources. Importantly, abnormal activity in the SN is implicated in various psychiatric disorders, including schizophrenia, anxiety disorders and major depressive disorders. The main nodes of the SN are the Anterior Cingulate Cortex (ACC), the Anterior Insular Cortex (AIC), the ventral striatum, ventral tegmental area, dorsomedial thalamus and the amygdala. These regions are anatomically and functionally connected. The experiments described in this proposal will delineate how the anatomical and functional connectivity these brain regions allow them to operate as a network. This proposal combines chemogenetic circuit-based manipulations with resting state functional magnetic resonance imaging (rs-fMRI), which measures the changes in hemodynamic signals in the brain. The goal of Specific Aim 1) Characterize the effects of chemogenetic ligands on resting state functional connectivity prior to viral expression of designer receptors exclusively activated by designer drugs (DREADDs). Because chemogenetic ligands can bind to non-DREADD receptors, this type of characterization is essential before proceeding with DREADD manipulations. In Specific Aim 2, I will combine DREADDs activation with rs-fMRI to target the ACC to probe the relationship between rs-functional connectivity and direct anatomical connections of the Salience Network. Understanding the relationship between the anatomy and the functional activity of the Salience Network will have implications for neuroimaging studies that have identified specific abnormalities in the Salience Network. Furthermore, these studies could detail generalizable rules for the biological relationship between anatomical and functional connectivity across the brain, which will have implications for understanding healthy and disordered brain functioning with the potential for developing novel treatments. This award will allow me to gain important skills in my PhD research. I will learn complex techniques, learn to design experiments, perform statistical analyses, write scientific manuscripts, and practice oral presentations of these studies. All of these will help prepare me for an academic faculty position.

项目概要 我们经常面临大量的刺激，这些刺激争夺有限的神经 资源。显着提示是重要且引人注目的提示。显着网络 (SN) 在不同条件下和休息时始终共同激活的一组大脑区域是 参与检测引起注意的外部和内部刺激，以适当地 分配认知资源。重要的是，SN 的异常活动与多种疾病有关。 精神疾病，包括精神分裂症、焦虑症和重度抑郁症 失调。 SN 的主要节点是前扣带皮层 (ACC)、前扣带皮层 (ACC) 岛叶皮质 (AIC)、腹侧纹状体、腹侧被盖区、背内侧丘脑和 杏仁核。这些区域在解剖学和功能上是相连的。实验 该提案中描述的将描述这些结构的解剖学和功能连接如何 大脑区域使它们能够像网络一样运作。 该提案将基于化学遗传学电路的操作与静息状态相结合 功能磁共振成像 (rs-fMRI)，可测量 大脑中的血流动力学信号。具体目标 1) 描述以下效果的特征 化学遗传学配体在病毒表达之前对静息态功能连接的影响 专门由设计药物（DREADD）激活的设计受体。因为化学遗传学 配体可以与非 DREADD 受体结合，这种类型的表征在 继续进行 DREADD 操作。在特定目标2中，我将结合DREADDs激活 使用 rs-fMRI 以 ACC 为目标，探讨 rs 功能连接与 显着网络的直接解剖连接。 了解解剖结构和功能活动之间的关系 显着网络将对神经影像学研究产生影响，这些研究已经确定了特定的 显着网络异常。此外，这些研究可以详细说明可推广的 跨器官的解剖学和功能连接之间的生物学关系的规则 大脑，这将对理解健康和紊乱的大脑功能产生影响 具有开发新疗法的潜力。 这个奖项将使我在博士研究中获得重要的技能。我会学习复杂的 技术，学习设计实验，进行统计分析，撰写科学论文 手稿，并练习这些研究的口头陈述。所有这些都将帮助我做好准备 担任学术教职。