A preoptic neuronal population controls fever and appetite during sickness

Area of Science:

• Neuroscience
• Immunology
• Physiology

Background:

• Infection triggers adaptive physiological and behavioral changes in animals.
• Common sickness symptoms include fever, warmth-seeking, fatigue, and appetite loss.
• The neural mechanisms coordinating these responses remain largely unknown.

Purpose of the Study:

• To identify neural populations involved in sickness responses.
• To elucidate the mechanisms by which the nervous system regulates fever and sickness behaviors.
• To understand how immune signals are integrated to orchestrate infection responses.

Main Methods:

• Single-nucleus RNA-sequencing.
• Multiplexed error-robust fluorescence in situ hybridization.
• Electrophysiological measurements.

Main Results:

• Identified a novel population of neurons in the ventral medial preoptic area (VMPO) activated by sickness-inducing agents (lipopolysaccharide, polyinosinic:polycytidylic acid).
• These VMPO neurons are essential for fever, warmth-seeking, and appetite loss.
• Demonstrated a paracrine mechanism involving immune signals activating VMPO neurons and revealed their broad influence on brain areas controlling behavior and homeostasis.

Conclusions:

• VMPO neurons act as a central hub integrating immune signals.
• These neurons orchestrate multiple sickness symptoms during infection.
• Uncovered a key neural circuit for coordinating sickness responses.