Poster abstracts
Poster number 80 submitted by Bradley Cutler
A PGE2 dependent shift in stimulus valence drives zebrafish behavioral fever
Bradley Cutler (The Ohio State University), Kaarthik A Balakrishnan (The Ohio State University), Jamie D Costabile (The Ohio State University), Claire Tobin, Hailey Hollins (The University of Utah), James Gagnon (The University of Utah)
Abstract:
Behavioral fever is therefore highly conserved across the animal kingdom. Unfortunately, we currently do not understand how inflammatory immune signals alter neural processing to drive animals towards warmer temperatures during fever. Here we established a behavioral fever paradigm in larval zebrafish after exposure to viral antigen (Poly I:C [dsRNA]). We could demonstrate that the conserved immune signaling molecule Prostaglandin E2 [PE2] is necessary for the establishment of behavioral fever in larval zebrafish. Furthermore, we mined existing zebrafish scRNAseq data and found that hypothalamic neurons express PE2 receptor transcripts. To locate these neurons, we used HCR in situ and discovered PE2 receptors in the POA, medulla, and habenula.
To identify changes in neural processing we performed calcium imaging in the medulla describing differential activity between saline and viral PAMP injected larval zebrafish. We found that hot neurons discovered in Balakrishnan et al. (2025) exhibit a significantly different expression profile when the organism is exposed to viral PAMPs. We were then able to use Markov models to simulate larval zebrafish behavior in the context of the calcium imaging. We described the “reversal mode” of larval zebrafish behavior and found that the simulated behavioral model shows much higher rates of cooling-stimulated swim reversals in PAMP exposed fish when compared to control. This strongly indicates a shift in the perceived valence of temperature stimuli during fever. Our research for the first time reveals how immune stimuli alter neural processing to drive seeking of warmer temperatures.
The neurological component of fever is still largely a mystery to medicine, and our new behavioral fever model makes important inroads for exploring these nuances. This enables the establishment of foundational scientific research, which could inspire new drugs or therapies for neurologically linked uncontrolled fever.
References:
Balakrishnan K, Haesemeyer M
Behavioral and circuit principles of temperature gradient navigation
Current Biology, 2025; 35, 5395-5410.e8
Keywords: temperature , fever, neural circuits