Temporal Specification of Basal Forebrain Circuitry

项目摘要 隔是基底前脑中的一种结构，在调节中起着关键作用 情绪状态包括恐惧、焦虑和抑郁。尽管我们越来越欣赏 对于侧间隔回路功能在调节情绪状态中的重要性，我们知道 对不同隔区神经元细胞类型的具体功能知之甚少，更少 关于创造这种多样性的发育机制。我们已经确定了 转录调控因子Prdm16(含正调控结构域16)，作为一种 调节外侧区不同亚型神经元产生的关键成分 隔膜。我们对Prdm16的研究是理解相关的 调节发育和规格的遗传程序和祖细胞类型 隔神经元亚型多样。在这项提案中，我们计划利用单细胞RNA 测序以绘制神经细胞的发育轨迹和整体多样性 隔膜上的类型。这些研究的结果将为 了解时间上特定的隔区神经元类型的发育和功能， 以及它们对行为回路的贡献。

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.