Speaker: Jessica Osterhout, University of Utah assistant professor of neurobiology

Title: "The neurobiology of sickness"

Abstract: During an infection, animals exhibit adaptive changes in behavior and physiology aimed at increasing survival. Although many causes of acute infection exist, a similar set of stereotyped symptoms occur, including increased body temperature or fever, increased pain sensitivity, decreased appetite, and decreased locomotion. Nearly all animals exhibit this adaptive response to infection, suggesting that circuits controlling sickness symptoms are hard-wired and highly conserved, yet exactly how the nervous system function is altered during systemic immune responses remains poorly understood. We have identified a population of neurons in the preoptic area of the hypothalamus that is activated following the administration of pro-inflammatory lipopolysaccharides (LPS). Using chemogenetic activation and cell ablation approaches we showed that this population affects fever initiation as well as other symptoms. Using viral-mediated tracing experiments and expression analysis, we identified direct and indirect downstream targets, providing a new understanding of homeostatic circuit modulation during infection. Single-cell sequencing, spatial transcriptomic, and neural activity analyses revealed a cellular and molecular mechanism leading to the direct activation of sickness-inducing neurons by locally produced immune molecules originating from specific non-neuronal cell types. Our results lead to a new model of how sickness symptoms are generated and how normal homeostatic circuits are altered during a state of acute sickness. Current work is focused on understanding how the brain senses an immune response and how additional symptoms, such as increased pain sensitivity, are controlled by a systemic infection.

Host: Dior Kelley, genetics, development and cell biology assistant professor