Poster abstracts

Poster number 11 submitted by Bradley Cutler

Determining the functional conservation of prostaglandin E2 signaling in zebrafish behavioral fever

Bradley Cutler (Molecular, Cellular, and Developmental Biology Program, The Ohio State University; Neuroscience Department), Kaarthik Abhinav Balakrishnan (The Ohio State University Neuroscience Department), Jamie D. Costable (The Ohio State University Neuroscience Department), Martin Haesemeyer (The Ohio State University Neuroscience Department)

Abstract:
If given the choice, vertebrates will prefer warmer environments when feeling ill; An effect that is highly conserved among all vertebrates. While endotherms can raise their body temperature independently of their environment, behavioral means of raising one’s body temperature remain the most energetically favorable (I.E. Finding a warmer room). However, the biochemical and neurocomputational programs that drive this differential behavior when antigen is detected remain undefined. For example, COX-2 (prostaglandin E2 (PE2) synthesis enzyme) and neural PE2 receptors are shown to be necessary for neurological inflammatory responses but the neurocomputational changes within both the hypothalamus and sensorimotor transformation circuits actuating differential thermoregulatory behaviors are unknown. Our research aims to elucidate these biochemical and neurocomputational drivers behind “behavioral fever”.

To address these questions, we have developed an assay to test the effects of inflammatory antigens on thermoregulatory behaviors. We allow 6-7 days-post-fertilization larvae to navigate a temperature gradient while we collect positional data. Our experiments show that when challenged with an inflammatory antigen, zebrafish larvae prefer warmer temperatures. This tells us larval zebrafish display behavioral fever; Therefore, behavior in a temperature gradient is an experimentally viable test for immune related shifts in temperature preference.

Through mining publicly available single-cell RNA-sequencing data we identified members of the prostaglandin E2 signaling cascade within expected cell types of the larval zebrafish hypothalamus. Experiments to determine the necessity of PE2 signaling in behavioral fever are underway using pharmacological approaches and knockouts. Once we establish a molecular framework, we will use fluorescent in-situ hybridization in addition to calcium imaging to determine the molecular and neurocomputational drivers of “behavioral fever”.

References:
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Keywords: Zebrafish, Animal Behavior, Neuroscience