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: 10464079
• 负责人: Adriana kelly-Ann Cushnie
• 金额: $ 4.37万
• 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/10464079
• 关键词: Acute; Agonist; Amygdaloid structure; Anatomy; Anterior; Anxiety Disorders; Attention; Award; Axon; Binding; Biological; Brain; Brain Diseases; Brain region; Cells; Clozapine; Cognitive; Comb animal structure; Communication; Complex; Cues; Data Analyses; Decision Making; Detection; Diagnosis; Disease; Doctor of Philosophy; Dose; Drug Receptors; Emotional; Etiology; Experimental Designs; Faculty; Functional Magnetic Resonance Imaging; Future; G-Protein-Coupled Receptors; 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; 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; base; 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; neuroimaging; neuropsychiatric disorder; nonhuman primate; novel; novel strategies; receptor; relating to nervous system; 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.

项目摘要 我们不断地面临着众多的刺激，竞争有限的神经 资源一个突出的线索是一个重要的和明显的。显著性网络（SN），a 一组在不同条件下和休息时持续共同激活的大脑区域， 参与注意力控制的外部和内部刺激的检测， 分配认知资源。重要的是，SN中的异常活动涉及多种疾病。 精神疾病，包括精神分裂症、焦虑症和重度抑郁症 紊乱SN的主要节点是前扣带皮层（ACC）、前扣带皮层（ACC）和前扣带皮层（ACC）。 岛叶皮层（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上和功能上是相互连接的。实验 在这个建议中描述的将描绘如何解剖和功能连接，这些 大脑区域使它们能够像网络一样运作。 该建议将基于化学发生回路的操作与静息状态相结合 功能性磁共振成像（rs-fMRI），它测量了 大脑中的血液动力学信号。具体目标的目标1）描述 在病毒表达之前，化学遗传配体对静息状态功能连接的影响 设计师受体专门由设计师药物激活（DREADDs）。因为化学基因 配体可以结合到非DREADD受体，这种类型的表征是必不可少的， 进行DREADD操作。在特殊目标2中，我将联合收割机DREADDs激活 用rs-fMRI靶向ACC，以探讨rs功能连接与 显著性网络的直接解剖学连接。 了解解剖和功能活动之间的关系， 显著性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 显著性网络中的异常此外，这些研究可以详细概括 跨组织的解剖和功能连接之间的生物学关系的规则 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。 这个奖项将使我在我的博士研究中获得重要的技能。我将学习复杂 技术，学习设计实验，进行统计分析，写科学 手稿，并练习口头介绍这些研究。所有这些都能帮助我 一个学术教师的职位