Date of Award
Summer 8-7-2026
Document Type
Dissertation
Publication Status
Version of Record
Submission Date
August 2026
Department
Biological Sciences
College Granting Degree
Charles E. Schmidt College of Science
Department Granting Degree
Biological Sciences
Degree Name
Doctor of Philosophy (PhD)
Thesis/Dissertation Advisor [Chair]
Ning Quan
Abstract
Interleukin-1β (IL-1β) is a well-established mediator of neuroinflammation in the developing brain, yet nearly all prior work has focused on the ligand while overlooking its receptor, IL-1R1. Because IL-1β can only act on cells that express IL-1R1, the neurons competent to respond to IL-1β during development, and the timing of that competence, have remained undefined. This dissertation addresses that gap by mapping neuronal IL-1R1 (nIL-1R1) across postnatal development and testing its function in circuit maturation.
Using a genetic reporter mouse line, I generated the first brain-wide spatiotemporal map of nIL-1R1 expression during the first three postnatal weeks. Rather than the restricted pattern seen in adults, the developing brain displayed highly organized, region-specific dynamics. Sensory relay nuclei showed transient "on/off" expression whose timing tracked the critical period of each modality, with the somatosensory and auditory pathways preceding the later-maturing visual pathway, while the dentate gyrus (DG) showed a progressive inside-out expansion and the raphe nuclei remained stable. Using unilateral whisker deprivation and tetrodotoxin silencing in the whisker-to-barrel pathway, I showed that nIL-1R1 expression in the barrel cortex is regulated by sensory input, establishing it as an activity-dependent gene.
Building on this map, I examined the function of nIL-1R1 in the DG-to-CA3 mossy fiber circuit. Chronic developmental blockade of neuronal IL-1R1 signaling selectively redistributed microglial engulfment of presynaptic glutamatergic material toward nIL-1R1-negative terminals without changing overall phagocytic activity, revealing a synapse-specific role in pruning. Blockade also shifted mossy fiber terminal morphology toward an immature, complex profile, recapitulating the IL-1R1-null phenotype, whereas postsynaptic dendritic spines were unaffected— demonstrating a presynaptic, compartment-specific effect.
Together, these findings establish nIL-1R1 as an activity-dependent participant in the maturation of postnatal neural circuits and define which circuits are positioned to respond to IL-1β during development. This work provides a foundation for understanding how early-life cytokine dysregulation may contribute to neurodevelopmental disorders.
Recommended Citation
Monet, Marianne Charlene, "NEURONAL IL-1R1 IN NEURODEVELOPMENT" (2026). Electronic Theses and Dissertations. 417.
https://digitalcommons.fau.edu/etd_general/417