Journal Article

A preoptic neuronal population controls fever and appetite during sickness

Zhuang, Xiaowei, Osterhout, Jessica A., Vaughn, Eric, Liu, Ding, Luo, Liqun, Dulac, Catherine, Moore, Jeffrey D., DeNardo, Laura A., Lee, Dean, Eichhorn, Stephen W., Kapoor, Vikrant

2022

Overview

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) 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 (VMPO LPS ) 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 VMPO LPS 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 VMPO LPS neurons as a control hub that integrates immune signals to orchestrate multiple sickness symptoms in response to infection. A newly identified population of neurons in the ventral medial preoptic area of the hypothalamus regulate stereotypical symptoms of illness, including fever and appetite suppression.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/51 / 14/1 / 14/32 / 38/39 / 38/77 / 38/91 / 631/378/371 / 631/378/3920 / 64/110 / 64/60 / 9/74 / Animals / Appetite - drug effects / Appetite Depressants - pharmacology / Appetite loss / Body temperature / Circuits / Cytokines / Fever / Fever - chemically induced / Fever - physiopathology / Fluorescence in situ hybridization / Gene expression / Gene sequencing / Humanities and Social Sciences / Hypothalamus / Illnesses / In Situ Hybridization, Fluorescence / Infections / Infections - chemically induced / Infections - physiopathology / Lipopolysaccharides / multidisciplinary / Nervous system / Neurogenesis / Neurons / Neurons - drug effects / Paracrine Communication / Paracrine signalling / Poly I-C / Population control / Preoptic area / Preoptic area (medial) / Preoptic Area - cytology / Preoptic Area - drug effects / Preoptic Area - physiology / Science / Science (multidisciplinary)