Temporal Specification of Basal Forebrain Circuitry

基底前脑回路的时间规范

• 批准号: 10550094
• 负责人: COREY C HARWELL
• 金额: $ 42.54万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10550094
• 关键词: Address; Aggressive behavior; Allium cepa; Anxiety; Behavior; Behavioral; Bipolar Depression; Bipolar Disorder; Birth Order; Brain region; Cells; Competence; Development; Developmental Gene; Electrophysiology (science); Embryo; Emotional; Foundations; Fright; Functional disorder; Gene Expression; Genes; Genetic; Genetic Transcription; Goals; Hippocampus (Brain); Histology; Knockout Mice; Lateral; Lead; Logic; Maps; Medial; Mediating; Mental Depression; Mental disorders; Molecular; Molecular Genetics; Molecular Profiling; Moods; Motivation; Neurons; Pathway interactions; Pattern; Play; Process; Production; Rabies virus; Research Proposals; Role; Schizophrenia; Septal Nuclei; Skin; Source; Specific qualifier value; Structure; Subgroup; Techniques; Testing; Time; basal forebrain; cell type; cholinergic; cohort; conditional knockout; insight; interdisciplinary approach; neurogenesis; neuropsychiatric disorder; new therapeutic target; progenitor; programs; sequencing platform; single-cell RNA sequencing; treatment strategy

Project Summary The septum is a structure in the basal forebrain that has critical roles in regulating emotional states including fear, anxiety and depression. Despite our growing appreciation for the importance of lateral septal circuit function in modulating emotional states, we know very little about the specific functions of the diverse septal neuron cell types and even less about the developmental mechanisms that create this diversity. We have identified the transcriptional regulator Prdm16 (Positive Regulatory Domain- containing 16), as being a critical component for regulating the production of distinct subtypes of neurons in the lateral septum. Our studies of Prdm16 serve as an entry point to understanding the relevant genetic programs and progenitor types regulating the development and specification of diverse septal neuron subtypes. In this proposal we plan to utilize single-cell RNA sequencing to map the developmental trajectories and overall diversity of neuronal cell types in the septum. The results from these studies will provide a foundation for understanding the development and function of temporally specified septum neuron types, and their contribution to behavioral circuits.

项目摘要 隔膜是基底前脑中的一个结构，在调节 情绪状态包括恐惧焦虑和抑郁尽管我们越来越欣赏 对于侧隔回路功能在调节情绪状态中的重要性，我们知道， 关于不同隔神经元细胞类型的具体功能， 创造这种多样性的发展机制。我们已经确定了 转录调节因子Prdm 16（含有正调节结构域的16），作为一种转录调节因子， 调节外侧神经元不同亚型产生的关键成分 隔膜我们对Prdm16的研究是了解相关 遗传程序和祖细胞类型调节的发展和规范 不同的隔神经元亚型。在这项提案中，我们计划利用单细胞RNA 测序以绘制神经元细胞的发育轨迹和总体多样性 隔膜中的类型。这些研究的结果将为 了解时间上特定的隔神经元类型的发育和功能， 以及它们对行为回路的贡献