Prefrontal Circuit Control of Isolation-Induced Aggression

孤立诱发攻击的前额叶回路控制

基本信息

  • 批准号:
    10638671
  • 负责人:
  • 金额:
    $ 67.24万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-03-06 至 2028-01-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY/ ABSTRACT Extended deprivation of social contact can produce deleterious effects on the brain and behavior. Social isolation (SI), or its perception (loneliness), is as predictive a risk factor for poor health outcomes as smoking or obesity. Many factors have contributed to a modern epidemic of loneliness: a growing aging population, dramatic changes to our social structure (technology, social media), the opioid crisis, and, most recently, the COVID-19 pandemic. One of the most damaging impacts of SI is the promotion of interpersonal aggression and violence against others – indeed, SI-associated domestic violence has risen by 20%, rates of suicide have surged, and school shootings continue to rip at the fabric of society. Despite this, we have a poor understanding of the genetically-defined, circuit mechanisms that give rise to isolation-induced aggression, representing a critical barrier for the development of targeted interventions and cognitive therapies to treat pathological forms of aggression. One key brain region known to exert top-down, cognitive control over behavior, including aggression, is the medial prefrontal cortex (mPFC). However, the role of the mPFC in modulating the effects of SI-induced aggression is unknown. In the project proposed here, we will interrogate the function of distinct, genetically-defined cells in the mPFC to modulate SI-induced aggression. In support of this, we recently identified the neuropeptide Tachykinin 2 (Tac2)/Neurokinin B (NkB) as a key, subcortical mediator of SI. Here, we will test whether Tac2 signaling in the mPFC exerts cortical control of SI-aggression. In preliminary studies, we have discovered that Tac2+ mPFC neurons comprise a unique, unexplored class of GABAergic interneurons (INs). These findings lead to the specific hypothesis that Tac2+ INs exert feed-forward inhibition of excitatory pyramidal neurons (PNs) to mediate SI-aggression. To test this, we will combine behavior, machine learning, molecular-genetic loss- and gain-of function manipulations, and in vivo Ca2+ imaging to achieve a circuit-level, mechanistic understanding of how distinct populations of genetically-defined neurons in the mPFC exert coordinated, cortical control of SI- aggression. We will determine whether mPFC Tac2+ neurons are required for SI-aggression (Aim 1), whether mPFC PNs are sufficient to inhibit SI-aggression (Aim 2), and whether Tac2+ INs directly regulate PN activity during SI-aggression (Aim 3). Collectively, we aim to uncover a conserved, genetically-defined mPFC microcircuit for the top-down, cortical control of isolation-induced aggression. These findings will transform the field by expanding our understanding of how pathological forms of aggression are encoded and controlled by prefrontal circuits in the brain. Importantly, this research will have profound implications for the treatment of social isolation-related mental health disorders, particularly those that result in violence.
项目概要/摘要 长期剥夺社交接触会对大脑和行为产生有害影响。社交隔离 (SI) 或其感知(孤独感)与吸烟或肥胖一样,是导致不良健康结果的危险因素。 许多因素导致了现代孤独感的流行:人口老龄化、巨大的变化 我们的社会结构(技术、社交媒体)、阿片类药物危机以及最近的 COVID-19 大流行。 SI 最具破坏性的影响之一是促进人际间的攻击和针对他人的暴力行为 – 事实上,与 SI 相关的家庭暴力上升了 20%,自杀率激增,校园枪击事件 继续撕裂社会结构。尽管如此,我们对基因定义的了解还很有限, 引起隔离引起的攻击的电路机制,代表了一个关键的障碍 开发有针对性的干预措施和认知疗法来治疗病理形式的攻击行为。一键 已知对行为(包括攻击性)施加自上而下的认知控制的大脑区域是内侧 前额皮质(mPFC)。然而,mPFC 在调节 SI 诱发的攻击行为中的作用是 未知。在这里提出的项目中,我们将询问不同的、基因定义的细胞的功能 mPFC 调节 SI 诱发的攻击行为。为了支持这一点,我们最近发现了神经肽速激肽 2 (Tac2)/神经激肽 B (NkB) 作为 SI 的关键皮层下调节因子。在这里,我们将测试 Tac2 信号是否在 mPFC 对 SI 攻击发挥皮质控制。在初步研究中,我们发现 Tac2+ mPFC 神经元由一类独特的、未经探索的 GABA 能中间神经元 (IN) 组成。这些发现导致 Tac2+ INs 对兴奋性锥体神经元 (PNs) 施加前馈抑制以介导的具体假设 SI-侵略。为了测试这一点,我们将结合行为、机器学习、分子遗传损失和增益 功能操作和体内 Ca2+ 成像,以实现对如何进行电路级、机制的理解 mPFC 中不同的基因定义的神经元群对 SI-发挥协调的皮质控制 侵略。我们将确定 mPFC Tac2+ 神经元是否需要 SI 攻击(目标 1),是否 mPFC PN 足以抑制 SI 攻击(目标 2),以及 Tac2+ IN 是否直接调节 PN 活性 SI 攻击期间(目标 3)。总的来说,我们的目标是发现一个保守的、基因定义的 mPFC 用于自上而下的皮层控制隔离引起的攻击的微电路​​。这些发现将改变 通过扩展我们对病理性攻击形式如何编码和控制的理解 大脑中的前额叶回路。重要的是,这项研究将对社会问题的治疗产生深远的影响。 与隔离相关的精神健康障碍,特别是那些导致暴力的疾病。

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 }}

Moriel Zelikowsky其他文献

Moriel Zelikowsky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('Moriel Zelikowsky', 18)}}的其他基金

Genetic dissection of neural circuits underlying trauma, fear, and social behavior
对创伤、恐惧和社会行为背后的神经回路进行基因剖析
  • 批准号:
    9978917
  • 财政年份:
    2019
  • 资助金额:
    $ 67.24万
  • 项目类别:
Genetic dissection of neural circuits underlying trauma, fear, and social behavior
对创伤、恐惧和社会行为背后的神经回路进行基因剖析
  • 批准号:
    9927083
  • 财政年份:
    2019
  • 资助金额:
    $ 67.24万
  • 项目类别:
Genetic dissection of neural circuits underlying trauma, fear, and social behavior
对创伤、恐惧和社会行为背后的神经回路进行基因剖析
  • 批准号:
    9319813
  • 财政年份:
    2016
  • 资助金额:
    $ 67.24万
  • 项目类别:

相似国自然基金

greenwashing behavior in China:Basedon an integrated view of reconfiguration of environmental authority and decoupling logic
  • 批准号:
  • 批准年份:
    2024
  • 资助金额:
    万元
  • 项目类别:
    外国学者研究基金项目

相似海外基金

Understanding the interplay between the gut microbiome, behavior and urbanisation in wild birds
了解野生鸟类肠道微生物组、行为和城市化之间的相互作用
  • 批准号:
    2876993
  • 财政年份:
    2027
  • 资助金额:
    $ 67.24万
  • 项目类别:
    Studentship
Collaborative Research: Chain Transform Fault: Understanding the dynamic behavior of a slow-slipping oceanic transform system
合作研究:链变换断层:了解慢滑海洋变换系统的动态行为
  • 批准号:
    2318855
  • 财政年份:
    2024
  • 资助金额:
    $ 67.24万
  • 项目类别:
    Continuing Grant
Collaborative Research: Subduction Megathrust Rheology: The Combined Roles of On- and Off-Fault Processes in Controlling Fault Slip Behavior
合作研究:俯冲巨型逆断层流变学:断层上和断层外过程在控制断层滑动行为中的综合作用
  • 批准号:
    2319848
  • 财政年份:
    2024
  • 资助金额:
    $ 67.24万
  • 项目类别:
    Standard Grant
Collaborative Research: Subduction Megathrust Rheology: The Combined Roles of On- and Off-Fault Processes in Controlling Fault Slip Behavior
合作研究:俯冲巨型逆断层流变学:断层上和断层外过程在控制断层滑动行为中的综合作用
  • 批准号:
    2319849
  • 财政年份:
    2024
  • 资助金额:
    $ 67.24万
  • 项目类别:
    Standard Grant
MCA Pilot PUI: From glomeruli to pollination: vertical integration of neural encoding through ecologically-relevant behavior
MCA Pilot PUI:从肾小球到授粉:通过生态相关行为进行神经编码的垂直整合
  • 批准号:
    2322310
  • 财政年份:
    2024
  • 资助金额:
    $ 67.24万
  • 项目类别:
    Continuing Grant
CAREER: A cortex-basal forebrain loop enabling task-specific cognitive behavior
职业:皮层基底前脑环路实现特定任务的认知行为
  • 批准号:
    2337351
  • 财政年份:
    2024
  • 资助金额:
    $ 67.24万
  • 项目类别:
    Continuing Grant
Conference: 2024 Photosensory Receptors and Signal Transduction GRC/GRS: Light-Dependent Molecular Mechanism, Cellular Response and Organismal Behavior
会议:2024光敏受体和信号转导GRC/GRS:光依赖性分子机制、细胞反应和生物体行为
  • 批准号:
    2402252
  • 财政年份:
    2024
  • 资助金额:
    $ 67.24万
  • 项目类别:
    Standard Grant
Nanoscopic elucidation of dynamic behavior of RNA viral nucleocapsid proteins using high-speed atomic force microscopy (HS-AFM)
使用高速原子力显微镜 (HS-AFM) 纳米级阐明 RNA 病毒核衣壳蛋白的动态行为
  • 批准号:
    24K18449
  • 财政年份:
    2024
  • 资助金额:
    $ 67.24万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
ERI: Data-Driven Analysis and Dynamic Modeling of Residential Power Demand Behavior: Using Long-Term Real-World Data from Rural Electric Systems
ERI:住宅电力需求行为的数据驱动分析和动态建模:使用农村电力系统的长期真实数据
  • 批准号:
    2301411
  • 财政年份:
    2024
  • 资助金额:
    $ 67.24万
  • 项目类别:
    Standard Grant
Understanding the synthesis and electronic behavior of beta tungsten thin film materials
了解β钨薄膜材料的合成和电子行为
  • 批准号:
    23K20274
  • 财政年份:
    2024
  • 资助金额:
    $ 67.24万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了