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 我们不断面临许多争夺有限神经的刺激 资源。显着的提示是重要且引人注目的提示。显着网络（SN）， 一组始终在不同条件和静止的情况下始终共激活的大脑区域 参与发现注意的外部和内部刺激的检测正确 分配认知资源。重要的是，SN中的异常活性与各种 精神疾病，包括精神分裂症，焦虑症和主要抑郁症 疾病。 SN的主要节点是前扣带回皮层（ACC） 岛状皮质（AIC），腹侧纹状体，腹侧侧侧区域，背部丘脑和 杏仁核。这些区域在解剖和功能上是连接的。实验 在本提案中描述的将描述解剖和功能连接如何 大脑区域允许它们作为网络运行。 该建议将基于化学发电的电路的操作与静止状态相结合 功能磁共振成像（RS-FMRI），可测量 大脑中的血液动力学信号。特定目标的目标1）表征 在静息状态功能连接之前，化学发生配体在病毒表达之前 设计器受体专门由设计师药物（Dreadds）激活。因为化学发生 配体可以与非二读受体结合，这种表征是必不可少的 进行恐惧的操纵。在特定的目标2中，我将结合Dreadds激活 使用RS-FMRI瞄准ACC，以探测RS功能连接和 显着网络的直接解剖联系。 了解解剖学与功能活性之间的关系 显着性网络将对已经确定特定的神经影像学研究产生影响 显着网络中的异常。此外，这些研究可以详细介绍可概括的 解剖与功能连接之间的生物学关系规则 大脑将对理解健康且无序的大脑功能有影响 有可能开发新疗法的潜力。 该奖项将使我能够在博士学位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，执行统计分析，写科学 这些研究的手稿和练习口头表现。所有这些都会帮助我做好准备 担任学术教师职位。