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

项目摘要/摘要 作为群居生物，社会互动对哺乳动物的健康至关重要。长期与社会脱节 环境可能导致社会孤立压力，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，人们对这些疾病背后的神经生物学知之甚少。 由社会孤立引起的变化，是该领域的一个关键差距。在这份提案中，我将调查 内侧前额叶皮质速激肽2表达中间神经元在调节中的作用 隔离诱导的攻击，通过基因特征、细胞类型特定功能的组合 操作和活体成像方法。我的初步工作建立了mPFC Tac2+神经元 并在雄性和雌性小鼠中发现了隔离诱导的攻击。在目标1中，我将使用一个就地 杂交法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同质的还是可以细分的 变成了亚群。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信号对隔离攻击是必要的，并将研究神经激肽B在 这一过程。最后，在目标3中，我将使用不同颜色钙的体内双色显微内窥镜成像 分别在mPFC Tac2+中间神经元和mPFC锥体神经元中表达的指标 这些神经元群体在隔离诱导的攻击中的活动。这个项目建立在我的强项之上 有啮齿动物行为的背景，并使我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 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，成为一家研究密集型机构的教授。通过了解 MPFC Tac2+中间神经元在隔离诱导攻击中的作用，这个项目将进一步推动我们的 了解长时间延长导致心理健康问题的电路水平机制 社会孤立。

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.