Circadian Regulation of Olfactory Modulation

West Virginia University Research Corporation, Morgantown WV

Investigators

Abstract

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.