Circadian Regulation of Olfactory Modulation

嗅觉调节的昼夜节律调节

• 批准号: 2114775
• 负责人: Andrew Dacks
• 金额: $ 50万
• 依托单位: West Virginia University Research Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2114775&HistoricalAwards=false
• 关键词: Circadian; Regulation; Olfactory; Modulation

Serotonin is a signaling model that is nearly ubiquitous both throughout the entire body and the animal kingdom. Within the brain, serotonergic neurons influence a wide array of neural processes and there is a rich history of exploration of the underlying consequences of serotonin at the molecular, cellular, and network levels. However, there remain many open questions about the contexts in which serotonin affects different features of healthy brain function, especially in sensory processing. This is in part due to the diversity of serotonergic neurons that differ in their intrinsic properties, the networks they influence and the mechanisms that regulate their activity. This project leverages the genetic accessibility and small number of neurons that can be reliably studied across individuals to explore the molecular and cellular regulatory mechanisms that underlie the interplay between serotonergic neurons and the daily rhythm of Drosophila melanogaster. This work will combine neuroanatomy, molecular biology and physiology to explore the behavioral consequences of interactions between the serotonergic system and neurons regulating daily activity rhythms. We will also use publicly available electron microscopy volumes of the brain of Drosophila to generate learning modules and instructor manuals to be implemented in biology classrooms to provide students with guided immersive experiences within large datasets.Serotonergic neurons project broadly throughout the nervous system, making them well positioned to influence many aspects of normal brain function. However, the cellular diversity of serotonergic neurons presents a challenge for understanding the context in which they will influence neural functions, including sensory processing. Using Drosophila melanogaster which has a small number of genetically accessible, identified serotonergic neurons, we will explore the molecular and cellular mechanisms that regulate the activity of two identified serotonergic neurons that project to multiple processing stages within the olfactory system. These two serotonergic neurons have been implied to be regulated by the circadian system in other species, but no circuit mechanisms for this are currently known. We will use molecular biology, neuroanatomy, neurophysiology and behavioral assays to determine how the clock network of the brain may influence these neurons, the consequence of these circuit interactions for the behavior and the consequences of regulation of serotonergic neurons for their downstream partners within the olfactory system. We will also use the Female Adult Fly Brain dataset to generate learning modules and instructor manuals that can be implemented in high school and undergraduate biology classrooms. These learning modules will expose students to different fields of cellular and molecular neuroscience by allowing users to be immersed in a large publicly available dataset with guided instruction as well as an open exploration component.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

血清素是一种几乎无处不在的信号模型，在整个身体和动物王国中都是如此。在大脑中，血清素能神经元影响广泛的神经过程，并且在分子，细胞和网络水平上对血清素的潜在后果进行了丰富的探索历史。然而，关于血清素影响健康大脑功能的不同特征的背景，特别是在感觉处理方面，仍有许多悬而未决的问题。这在一定程度上是由于血清素能神经元的多样性，这些神经元在其内在特性、其影响的网络和调节其活动的机制方面存在差异。本项目利用遗传可及性和可在个体间可靠研究的少量神经元，探索5 -羟色胺能神经元与黑腹果蝇日常节律之间相互作用的分子和细胞调节机制。这项工作将结合神经解剖学、分子生物学和生理学来探索血清素能系统和调节日常活动节奏的神经元之间相互作用的行为后果。我们还将使用公开可用的果蝇大脑电子显微镜体积来生成学习模块和指导手册，以便在生物学教室中实施，为学生提供大型数据集中的引导沉浸式体验。5 -羟色胺能神经元在整个神经系统中广泛分布，使它们能够很好地影响正常大脑功能的许多方面。然而，5 -羟色胺能神经元的细胞多样性对理解它们影响神经功能（包括感觉处理）的背景提出了挑战。以黑腹果蝇（Drosophila melanogaster）为研究对象，我们将探索调节两种已识别的血清素能神经元活动的分子和细胞机制，这两种神经元可以在嗅觉系统的多个处理阶段进行投射。在其他物种中，这两种血清素能神经元被认为受昼夜节律系统的调节，但目前尚不清楚这一机制的电路机制。我们将使用分子生物学，神经解剖学，神经生理学和行为分析来确定大脑的时钟网络如何影响这些神经元，这些回路相互作用对行为的后果以及嗅觉系统中下游伙伴调节血清素能神经元的后果。我们还将使用雌性成年果蝇大脑数据集来生成学习模块和讲师手册，这些模块和手册可以在高中和本科生物学课堂上实施。这些学习模块将让学生接触到细胞和分子神经科学的不同领域，允许用户沉浸在一个大型的公开可用的数据集中，并提供指导和开放的探索组件。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。