Circadian Regulation of Olfactory Modulation

5-羟色胺是一种信号传导模型，在整个身体和动物王国中几乎无处不在。在脑内，5-羟色胺能神经元影响广泛的神经过程，并且在分子、细胞和网络水平上探索5-羟色胺的潜在后果有着丰富的历史。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，仍然存在许多悬而未决的问题。这在一定程度上是由于多巴胺能神经元的多样性，这些神经元在其内在特性、它们影响的网络以及调节其活性的机制方面不同。该项目利用遗传可及性和少量神经元，可以在个体之间进行可靠的研究，以探索神经元能神经元与果蝇日常节律之间相互作用的分子和细胞调控机制。这项工作将结合联合收割机神经解剖学，分子生物学和生理学，探索行为的后果之间的相互作用的神经系统和神经元调节日常活动的节奏。我们还将使用公开的果蝇大脑的电子显微镜卷来生成学习模块和教师手册，这些模块和手册将在生物课堂上实施，为学生提供大型数据集内的指导沉浸式体验。5-羟色胺能神经元广泛地投射在整个神经系统中，使它们能够很好地影响正常大脑功能的许多方面。然而，多巴胺能神经元的细胞多样性对理解它们将影响神经功能（包括感觉处理）的背景提出了挑战。使用果蝇，其中有一个小数目的遗传可访问的，确定的多巴胺能神经元，我们将探讨调节两个确定的多巴胺能神经元，项目的嗅觉系统内的多个处理阶段的活动的分子和细胞机制。这两种多巴胺能神经元在其他物种中被暗示受昼夜节律系统的调节，但目前还没有已知的电路机制。我们将使用分子生物学，神经解剖学，神经生理学和行为测定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影响，以及嗅觉系统内下游伙伴的多巴胺能神经元调节的影响。我们还将使用女性成年苍蝇大脑数据集来生成可以在高中和本科生物课堂中实施的学习模块和教师手册。这些学习模块将使学生接触到细胞和分子神经科学的不同领域，让用户沉浸在一个大型的公开数据集中，并提供指导性指导和开放式探索组件。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。

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.