Author ORCID Identifier
Semester
Summer
Date of Graduation
2026
Document Type
Dissertation
Degree Type
PhD
College
Eberly College of Arts and Sciences
Department
Biology
Committee Chair
Andrew M. Dacks
Committee Member
Sadie A. Bergeron
Committee Member
Kevin Daly
Committee Member
Alex Keene
Committee Member
Gary Marsat
Abstract
Sleep is a fundamental process for survival as it facilitates and protects memory consolidation, cellular waste clearance, and energy homeostasis. Therefore, it is important that once sleep is initiated it is only disrupted under critical circumstances. Sleep drive accumulates as we experience the world around us, but the sleeping brain also remains vigilant to salient stimuli. Thus, sensory processing modulates both sleep initiation and architecture. Perhaps unsurprisingly, sensory dysfunction is one of the largest contributors to disrupted sleep in children and adults, with nearly every sensory modality having an effect on sleep. In mammals, it is thought that the majority of sensory modalities are routed through thalamocortical pathways to modulate sleep/wake states, suggesting that thalamic circuits are a central gating mechanism for sleep quality. Olfaction, or the sense of smell, does not directly contact the thalamus, yet olfactory dysfunction severely impairs sleep quality and may even increase the risk of developing sleep disorders. However, the fundamental principles by which olfactory signaling in the brain modulates sleep is unclear. Considering not every odor has a uniform effect on sleep quality, and individuals with olfactory dysfunction experience a variety of sleep phenotypes, these findings suggest that distinct olfactory pathways modulate different parameters of sleep. This is consistent with the combinatorial and identity/value-based nature in which olfactory signals are processed. To better understand the mechanisms by which olfaction modulates sleep, it is imperative to interrogate the olfactory system in a genetical tractable animal model with pre-defined olfactory circuitry. In this dissertation, I leverage the genetic toolbox of the fruit fly Drosophila melanogaster to characterize how broad olfactory dysfunction and dysfunction tailored to individual olfactory pathways impair both baseline sleep architecture and olfactory arousal. I, like others, show that olfactory receptor neurons (ORNs), which transduce olfactory information from the environment, are a key cell type promoting olfactory modulation of sleep. Namely, the neurotransmission of distinct but broad classes of ORNs contribute to sleep differently, in that some ORNs modulate day sleep, while others modulate night. Interestingly, the transmission from individual ORN types that make up these broad classes do not necessarily reflect the broader loss of function phenotypes, suggesting that individual olfactory pathways may be differentially regulated within the context of sleep. Indeed, I show that known modulators of ORN activity, such as serotonin (5-HT), promote many of the heterogeneous effects of ORNs within the context of sleep, suggesting that 5-HT may act in the periphery as a form of sensory gaining or gating depending on the local circuit it is released within. I further investigate this hypothesis and show that odors presented during the day elicit different levels of arousal than ones in the nighttime. Additionally, 5-HT signaling attenuates or enhances arousal depending on the cell type and receptor pathways being utilized. Together, this work provides insight into the cellular and molecular mechanisms bridging olfaction and sleep and provides a circuit framework that can be leveraged to continue characterizing the consequences of sensory dysfunction on behavior.
Recommended Citation
Cook, Oliver Mason, "Serotonin signaling within the olfactory network heterogeneously modulates sleep architecture and arousal" (2026). Graduate Theses, Dissertations, and Problem Reports (ETD). 13379.
https://researchrepository.wvu.edu/etd/13379