A preoptic neuronal population controls fever and appetite during sickness

Jessica A. Osterhout, Vikrant Kapoor, Stephen W. Eichhorn, Eric Vaughn, Jeffrey D. Moore, Ding Liu, Dean Lee, Laura A. DeNardo, Liqun Luo, Xiaowei Zhuang and Catherine Dulac ()
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Jessica A. Osterhout: Harvard University
Vikrant Kapoor: Harvard University
Stephen W. Eichhorn: Harvard University
Eric Vaughn: Harvard University
Jeffrey D. Moore: Harvard University
Ding Liu: Harvard University
Dean Lee: Harvard University
Laura A. DeNardo: Stanford University
Liqun Luo: Stanford University
Xiaowei Zhuang: Harvard University
Catherine Dulac: Harvard University

Nature, 2022, vol. 606, issue 7916, 937-944

Abstract: Abstract During infection, animals exhibit adaptive changes in physiology and behaviour aimed at increasing survival. Although many causes of infection exist, they trigger similar stereotyped symptoms such as fever, warmth-seeking, loss of appetite and fatigue1,2. Yet exactly how the nervous system alters body temperature and triggers sickness behaviours to coordinate responses to infection remains unknown. Here we identify a previously uncharacterized population of neurons in the ventral medial preoptic area (VMPO) of the hypothalamus that are activated after sickness induced by lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid. These neurons are crucial for generating a fever response and other sickness symptoms such as warmth-seeking and loss of appetite. Single-nucleus RNA-sequencing and multiplexed error-robust fluorescence in situ hybridization uncovered the identity and distribution of LPS-activated VMPO (VMPOLPS) neurons and non-neuronal cells. Gene expression and electrophysiological measurements implicate a paracrine mechanism in which the release of immune signals by non-neuronal cells during infection activates nearby VMPOLPS neurons. Finally, we show that VMPOLPS neurons exert a broad influence on the activity of brain areas associated with behavioural and homeostatic functions and are synaptically and functionally connected to circuit nodes controlling body temperature and appetite. Together, these results uncover VMPOLPS neurons as a control hub that integrates immune signals to orchestrate multiple sickness symptoms in response to infection.

Date: 2022
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DOI: 10.1038/s41586-022-04793-z

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