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

项目摘要 我们不断地面对大量的刺激，这些刺激争夺有限的神经 资源。突出的提示是重要的和引人注目的提示。显著网络(SN)、 一组在不同条件下和静止时持续共同激活的大脑区域，是 参与对引起注意的外部和内部刺激的正确检测 分配认知资源。重要的是，SN中的异常活动与多种疾病有关 精神障碍，包括精神分裂症、焦虑症和严重抑郁 精神错乱。前扣带回的主要结节是前扣带回、前扣带回、前扣带回 岛叶皮质、腹侧纹状体、腹侧被盖区、背内侧丘脑和 杏仁核。这些区域在解剖上和功能上是相连的。这些实验 这份提案中描述的将描绘这些解剖和功能连接如何 大脑区域使它们能够像一个网络一样运作。 该方案将基于化学发生电路的操作与静止状态相结合 功能磁共振成像(rs-fMRI)，它测量的变化在 大脑中的血液动力学信号。具体目标的目标1)描述 病毒表达前静息状态功能连通性的化学发生配体 设计师受体仅由设计师药物(DREADD)激活。因为化学发生 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。在具体目标2中，我将结合DREADDS激活 应用RS-fMRI靶向ACC，探讨RS-功能连接性与 凸起网络的直接解剖联系。 了解解剖学和大脑功能活动之间的关系 显著网络将对神经成像研究产生影响，这些研究已经确定了特定的 显著网络中的异常。此外，这些研究可以详细说明可概括性 人体解剖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。我会学复杂的 技术，学会设计实验，进行统计分析，撰写科学 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 申请一个学术教员的职位。

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.