Genetic dissection of lateral septal circuitry that controls stress-induced persistent anxiety states

控制压力引起的持续焦虑状态的外侧间隔电路的基因解剖

基本信息

  • 批准号:
    10748497
  • 负责人:
  • 金额:
    $ 8.56万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-03-01 至 2023-12-31
  • 项目状态:
    已结题

项目摘要

Project Summary We are investigating the neural circuits that control persistent elevations of defensive behaviors following uncontrollable stress. This has potential human health benefits relevant to the mission of the NIH. In particular, exposure to uncontrollable stress is thought to contribute to or directly trigger the onset of multiple psychiatric disorders for which existing therapies are inadequate. Improved treatments for such disorders will require an understanding of how stressful experiences normally engage specific neural circuits to increase anxiety and defensive behaviors, as well as how abormal engagement of these circuits leads to mental illness. Corticotropin releasing factor receptors (CRFR) control behavioral and physiological responses to stress and are implicated in trauma-related mental illnesses, but the neural circuit-level mechanisms by which they act have not been clearly defined. One critically important region is the lateral septum (LS), which is potently activated by uncontrollable stressors and regulates severity of stress-induced anxious states via the type 2 CRFR (CRFR2) in rodent models. Moreover, neuroimaging studies of patients with stress-related disorders have consistently detected abnormalities in the hippocampus, a structure that is strongly connected with the LS. However, the precise means by which stress induces persistent CRFR2-dependent changes in anxiety and defensive behaviors via specific LS circuits, and the potential roles of hippocampal inputs, have not been determined. Here, we focus on filling this gap in knowledge by addressing two fundamentally important issues concerning LS connectivity and function in the mouse, a model organism whose brain shares high structural and molecular similarity to the human brain. In Aim 1, we will determine how activity of CRFR2-expressing neurons in LS changes following a stressful experience, and how these changes are related to the severity of stress-induced anxious behavior. As particular patterns of neural activity may promote resilience or susceptibility to stress, this aim has the potential to inform new approaches to prevent or treat stress-related disorders. We will also determine how the CRFR2 receptor alters activity of LS neurons. This is important as efforts to treat stress-related mental illnesses by administering drugs that act on CRF receptors have shown some promise but have had limited success. An improved understanding of how CRF receptors control brain activity may therefore result in development of more effective therapies. In Aim 2, we will determine how a specific input from the hippocampus is connected to the LS, responds to threat, and influences anxiety and fear-related behaviors.
项目摘要 我们正在研究控制以下防御行为持续升高的神经回路 无法控制的压力。这对人类健康具有潜在的益处,与美国国立卫生研究院的使命相关。特别是, 暴露在无法控制的压力下被认为是导致或直接引发多发性精神分裂症的原因 现有治疗方法不足以治疗的疾病。改善对这类疾病的治疗将需要 了解应激经历通常如何激活特定的神经回路来增加焦虑和 防御性行为,以及这些回路的异常参与如何导致精神疾病。 促肾上腺皮质激素释放因子受体(CRFR)控制应激的行为和生理反应,并 与创伤相关的精神疾病有关,但它们的神经回路水平机制 都没有明确的定义。外侧隔(LS)是一个非常重要的区域,它是 被不可控的应激源激活,并通过2型调节应激诱导的焦虑状态的严重性 CRFR(CRFR2)在啮齿动物模型中的表达。此外,应激相关障碍患者的神经成像研究 一直检测到海马体的异常,海马体是一种与 LS.然而,应激导致焦虑和焦虑中CRFR2持续依赖的变化的确切方式 通过特定LS回路的防御行为,以及海马区输入的潜在作用,还没有得到 下定决心。在这里,我们通过解决两个根本上重要的问题来填补这一知识空白 关于小鼠的LS连通性和功能,一个其大脑共享高结构的模式生物 以及与人脑的分子相似性。 在目标1中,我们将确定在应激后LS中表达CRFR2的神经元的活动如何变化 经验,以及这些变化如何与压力诱导的焦虑行为的严重程度相关。AS 神经活动的特定模式可能会促进对压力的弹性或敏感性,这一目标具有潜在的 为预防或治疗压力相关疾病提供新的方法。我们还将确定CRFR2如何 受体改变LS神经元的活动。这一点很重要,因为通过以下方式治疗与压力相关的精神疾病 使用作用于CRF受体的药物显示了一些希望,但收效甚微。一个 因此,对CRF受体如何控制大脑活动的更好理解可能会导致 更有效的治疗方法。 在目标2中,我们将确定来自海马体的特定输入如何连接到LS,响应 威胁,并影响焦虑和恐惧相关的行为。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Thomas L. Schwarz其他文献

Discovery of small molecule pathway regulators by image 2 profile matching
通过图像 2 配置文件匹配发现小分子途径调节剂
  • DOI:
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    0
  • 作者:
    M. Rohban;Ashley M. Fuller;Ceryl Tan;Jonathan T. Goldstein;Deepsing Syangtan;Madhura P. Nijsure;M. Rigby;Joshua R. Sacher;S. M. Corsello;Grace B. Peppler;Marta;Bogaczynska;Gabrielle E Ciotti;Ann DeVine;M. Doan;Jennifer P. Gale;Rik Derynck;T. Turbyville;J. Boerckel;Shantanu Singh;L. Kiessling;Thomas L. Schwarz;X. Varelas;Ran Kafri;T. S. Eisinger;Anne E Carpenter
  • 通讯作者:
    Anne E Carpenter

Thomas L. Schwarz的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Thomas L. Schwarz', 18)}}的其他基金

Kinetochore Protein Functions in Synaptogenesis
动粒蛋白在突触发生中的功能
  • 批准号:
    10891859
  • 财政年份:
    2023
  • 资助金额:
    $ 8.56万
  • 项目类别:
Genetic dissection of lateral septal circuitry that controls stress-induced persistent anxiety states
控制压力引起的持续焦虑状态的外侧间隔电路的基因解剖
  • 批准号:
    10542797
  • 财政年份:
    2019
  • 资助金额:
    $ 8.56万
  • 项目类别:
Kinetochore Protein Functions in Synaptogenesis
动粒蛋白在突触发生中的功能
  • 批准号:
    10248433
  • 财政年份:
    2019
  • 资助金额:
    $ 8.56万
  • 项目类别:
Kinetochore Protein Functions in Synaptogenesis
动粒蛋白在突触发生中的功能
  • 批准号:
    10017352
  • 财政年份:
    2019
  • 资助金额:
    $ 8.56万
  • 项目类别:
Axonal Transport of mRNA for Mitochondrial Proteins
线粒体蛋白 mRNA 的轴突运输
  • 批准号:
    10210451
  • 财政年份:
    2018
  • 资助金额:
    $ 8.56万
  • 项目类别:
Axonal Transport of mRNA for Mitochondrial Proteins
线粒体蛋白 mRNA 的轴突运输
  • 批准号:
    9921501
  • 财政年份:
    2018
  • 资助金额:
    $ 8.56万
  • 项目类别:
Axonal Transport of mRNA for Mitochondrial Proteins
线粒体蛋白 mRNA 的轴突运输
  • 批准号:
    10430133
  • 财政年份:
    2018
  • 资助金额:
    $ 8.56万
  • 项目类别:
Developmental Neurology
发育神经病学
  • 批准号:
    9385084
  • 财政年份:
    2017
  • 资助金额:
    $ 8.56万
  • 项目类别:
2016 Cell Biology of the Neuron Gordon Research Conference and Gordon Research Seminar
2016年神经元细胞生物学戈登研究会议暨戈登研究研讨会
  • 批准号:
    9193674
  • 财政年份:
    2016
  • 资助金额:
    $ 8.56万
  • 项目类别:
Developmental Neurology
发育神经病学
  • 批准号:
    9385080
  • 财政年份:
    2016
  • 资助金额:
    $ 8.56万
  • 项目类别:

相似海外基金

How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 8.56万
  • 项目类别:
    Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 8.56万
  • 项目类别:
    Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 8.56万
  • 项目类别:
    Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 8.56万
  • 项目类别:
    Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 8.56万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 8.56万
  • 项目类别:
    Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 8.56万
  • 项目类别:
    Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 8.56万
  • 项目类别:
    Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
  • 批准号:
    23K00129
  • 财政年份:
    2023
  • 资助金额:
    $ 8.56万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
  • 批准号:
    2883985
  • 财政年份:
    2023
  • 资助金额:
    $ 8.56万
  • 项目类别:
    Studentship
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了