Biology ETDs

Publication Date

Summer 7-15-2022

Abstract

Olfactory sensory neurons (OSNs) directly contact the environment and are

exposed to pathogens, such as viruses. When OSNs detect a virus, they coordinate antiviral immune responses locally to stop virus progression into the brain, termed the central nervous system (CNS). For example, in COVID-19 patients the SARS-CoV-2 virus replicates in the olfactory epithelium resulting in loss of olfaction, yet viral presence in the CNS is rare. However, neuronal detection of a virus by OSNs may send electrical signals to the CNS via the olfactory bulb (OB) and shape our CNS. Because the OB is the nexus between the pathogen exposed olfactory epithelium and the vulnerable CNS, itis a hotspot for

cooperation between neurons and immune cells. We identify a direct interaction between a virus and OSNs in rainbow trout, and report antiviral immune responses in the OB, even without virus reaching to the OB. How neuronal signals trigger immune responses in the OB is not understood. The goal of this project is to understand how viral detection by OSNs mediates neuroimmune responses in a

brain region, the OB. Preliminary data in a genetically pliable model, zebrafish

(Danio rerio), demonstrates viral-specific neuronal activation of OSNs projecting into the OB, suggesting that OSNs are electrically activated by viruses. Further,

behavioral changes can be seen in both adult and larval zebrafish immediately

after viral exposure. By profiling the transcription of single cells in the OB after

OSNs are exposed to virus, we found that both immune cells of the CNS, known as microglia, and neurons enter a protective state. This protective state is characterized by a decrease in gene expression of neuronal differentiation factors and an onset of innate immune response mediators. Thus, neurons in the OB appear to increase neuronal precursor status when a virus in detected in the

olfactory epithelium. We finally identify a new immune surveillance mechanism in the olfactory-brain axis, innate T cells that intimately associate with the olfactory nerve and respond to peripheral damage. Combined, this work reveals how encounters with viruses in our nose throughout our lifetime may shape neuronal identity in our brains and result in behavioral responses in ways previously unrecognized.

Language

English

Document Type

Thesis

Degree Name

Biology

Level of Degree

Doctoral

Department Name

UNM Biology Department

First Committee Member (Chair)

Irene Salinas

Second Committee Member

Eric Denkers

Third Committee Member

Kiran Bhaskar

Fourth Committee Member

Isaac Chiu

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