Student Theses and Dissertations

Date of Award

2024

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Thesis Advisor

Cori Bargmann

Keywords

serotonin, C. elegans, sickness behavior, pathogen avoidance, neuromodulation, HSN neurons

Abstract

Serotonin is an ancient and powerful neuromodulator that regulates diverse processes from fundamental physiology to complex emotions. Due to the many functions of serotonin distributed throughout the body and brain, governing principles of serotonin signaling have remained elusive. There is particular interest in how serotonin modulates internal states given that serotonin dysregulation is a feature of many psychiatric diseases. In this thesis, I use the simplified serotonergic system of C. elegans to explore how serotonin governs the internal state of sickness. In addition to activating the immune system and remodeling physiology, pathogenic infection results in adaptive behavioral changes that promote survival. These 'sickness behaviors' are observed throughout the animal kingdom. I induced sickness in C. elegans by exposing them to a lawn of pathogenic bacteria, and then studied how avoidance behaviors developed over time. Animals slowly developed an aversion to the pathogen, and avoidance of a bacterial lawn over multiple hours. This behavior is delayed and reduced in mutants deficient in serotonin synthesis. I found that serotonin synthesis in two distinct neuronal cell types promotes pathogen avoidance at different stages of development. In L4-stage larvae, serotonin synthesized by NSM neurons in the pharynx increases avoidance of pathogenic bacteria. In adult animals, HSN neurons produce the serotonin required for acquired pathogen avoidance. Using a machine learning pipeline to track animals over a 20-hour assay, I characterized animals' dynamic interactions with the edge of the pathogenic bacterial lawn. Serotonin synthesized by HSN neurons promotes exit and repulsion from the pathogenic bacteria and suppresses re-entry into the pathogen lawn. HSN neurons regulate egg-laying behavior, and when exposed to pathogen, animals are more likely to lay eggs in the absence of food than uninfected animals. These results suggest that in the pathogen context, HSN neurons are more active in the absence of bacteria. My results demonstrate that sickness-induced changes in serotonin signaling from neurons promote adaptive pathogen avoidance behavior.

Comments

A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy

License and Reuse Information

Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License
This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 International License.

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