Top‐Down Control of Isolation‐Induced Aggression Through mPFC Tac2+ Interneurons

上-下隔离控制-通过 mPFC Tac2 中间神经元诱导攻击

基本信息

批准号：
10536007
负责人：
Rachel Gatlin
金额：
$ 3.69万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-01 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10536007
关键词：
Adolescent Aggressive behavior Anxiety Behavior Behavioral Biological Assay Brain Brain region COVID-19 pandemic Calcium Chronic Color Computer Analysis Confocal Microscopy Data Data Analyses Development Equilibrium Exhibits Feeling Fellowship Female Genes Genetic Genetic Identity Goals Health House mice Image In Situ Hybridization Institution Interneurons Knowledge Lead Link Measures Medial Mediating Mental Depression Mental Health Modeling Mus Neurobiology Neurokinin B Neuromedin K Receptor Neurons Neuropeptides Neurosciences Operative Surgical Procedures Outcome Pattern Population Positioning Attribute Prefrontal Cortex Process Public Health Research Rodent Role Signal Transduction Social Environment Social Interaction Social isolation Stress System Tachykinin Technical Expertise Testing Training Violence Viral Work base calcium indicator career cell type gamma-Aminobutyric Acid hippocampal pyramidal neuron imaging approach implantation in vivo in vivo imaging insight knock-down lens loss of function male microendoscopy neural correlate novel professor skills social social separation stressor

项目摘要

Project Summary/Abstract As social creatures, social interaction is vital for mammalian health. Prolonged separation from social environments can result in social isolation stress, which is linked to poor mental health outcomes, including anxiety, depression, and violence. Despite this, relatively little is known about the neurobiology underlying these changes induced by social isolation, representing a critical gap in the field. In this proposal, I will investigate the role of Tachykinin 2-expressing (Tac2+) interneurons in the medial prefrontal cortex (mPFC) in regulating isolation-induced aggression, through a combination of genetic characterization, cell-type specific functional manipulations, and in vivo imaging approaches. My preliminary work establishes mPFC Tac2+ neurons as interneurons and finds isolation-induced aggression in both male and female mice. In Aim 1 I will use an in situ hybridization assay to investigate the extent to which neuropeptide-encoding genes are expressed in mPFC Tac2+ interneurons to understand whether these neurons are a homogenous population or can be subdivided into subpopulations. Then, in Aim 2 I will examine whether the activity of mPFC Tac2+ interneurons or Tac2/Neurokinin B signaling is necessary for isolation-aggression and will investigate the role of neurokinin B in this process. Lastly in Aim 3, I will use dual-color in vivo microendoscopic imaging of different colored calcium indicators expressed in mPFC Tac2+ interneurons and mPFC pyramidal neurons, respectively, to understand the activity of these neuronal populations during isolation-induced aggression. This project builds off my strong background in rodent behavior and allows me to gain computational skills for the analysis of behavior and calcium imaging data. Under the training provided by this fellowship, I will gain the necessary technical skills, knowledge of my field, and data analysis skills to assist in my transition to a postdoctoral position in systems neuroscience and achieve my career goal of becoming a professor at a research-intensive institution. Through understanding the contribution of mPFC Tac2+ interneurons to isolation-induced aggression, this project will further our understanding of the circuit-level mechanisms that contribute to mental health issues resulting from prolonged social isolation.

项目概要/摘要作为社会性动物，社会互动对于哺乳动物的健康至关重要。长期与社交隔离环境会导致社会孤立压力，这与不良的心理健康结果有关，包括焦虑、抑郁和暴力。尽管如此，人们对这些现象背后的神经生物学知之甚少。社会隔离引起的变化代表了该领域的一个关键差距。在这个提案中，我将调查内侧前额叶皮质 (mPFC) 中表达速激肽 2 (Tac2+) 的中间神经元在调节中的作用隔离诱导的攻击性，通过遗传特征、细胞类型特定功能的组合操作和体内成像方法。我的初步工作将 mPFC Tac2+ 神经元建立为中间神经元并在雄性和雌性小鼠中发现了隔离引起的攻击行为。在目标 1 中，我将使用原位杂交测定研究神经肽编码基因在 mPFC 中的表达程度 Tac2+ 中间神经元，以了解这些神经元是否是同质群体或可以细分进入亚人群。然后，在目标 2 中，我将检查 mPFC Tac2+ 中间神经元或 Tac2/神经激肽 B 信号传导对于孤立攻击是必需的，并将研究神经激肽 B 在这个过程。最后在目标 3 中，我将使用不同颜色钙的双色体内显微内窥镜成像分别在 mPFC Tac2+ 中间神经元和 mPFC 锥体神经元中表达的指标，以了解这些神经元群在隔离引起的攻击期间的活动。这个项目增强了我的实力啮齿动物行为背景，使我能够获得分析行为和钙的计算技能成像数据。在该奖学金提供的培训下，我将获得必要的技术技能、知识我的领域的知识和数据分析技能，以帮助我过渡到系统神经科学的博士后职位并实现我的职业目标，成为研究密集型机构的教授。通过了解 mPFC Tac2+ 中间神经元对隔离引起的攻击行为的贡献，该项目将进一步促进我们的研究了解导致长期心理健康问题的电路级机制社交隔离。