4.8 Article

A preoptic neuronal population controls fever and appetite during sickness

Journal

NATURE
Volume 606, Issue 7916, Pages 937-+

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41586-022-04793-z

Keywords

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Funding

  1. NIH [R01NS112399]
  2. Simons Foundation [572189]

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This study identifies a previously uncharacterized population of neurons in the brain that are activated after infection, playing a crucial role in generating fever response and other sickness symptoms. By examining gene expression and electrophysiological measurements, the researchers uncover a mechanism where these neurons are influenced by immune signals released by non-neuronal cells during infection and are functionally connected to brain areas controlling body temperature and appetite.
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 fatigue(1,)(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) ofthe 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 VMPO(LPS )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.

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