Preoptic EP3R neurons constitute a two-way switch for fever and torpor

Natalia L. S. Machado (), Nicole Lynch, Luis H. A. Costa, David Melville, Hakan Kucukdereli, Satvinder Kaur, Alexander S. Banks, Francesca Raffin, Oscar D. Ramirez-Plascencia, Sydney Aten, Janayna D. Lima, Sathyajit S. Bandaru, Richard D. Palmiter and Clifford B. Saper ()
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Natalia L. S. Machado: Beth Israel Deaconess Medical Center and Division of Sleep Medicine and Program in Neuroscience, Harvard Medical School
Nicole Lynch: Beth Israel Deaconess Medical Center and Division of Sleep Medicine and Program in Neuroscience, Harvard Medical School
Luis H. A. Costa: Beth Israel Deaconess Medical Center and Division of Sleep Medicine and Program in Neuroscience, Harvard Medical School
David Melville: Beth Israel Deaconess Medical Center and Division of Sleep Medicine and Program in Neuroscience, Harvard Medical School
Hakan Kucukdereli: Beth Israel Deaconess Medical Center and Harvard Medical School
Satvinder Kaur: Beth Israel Deaconess Medical Center and Division of Sleep Medicine and Program in Neuroscience, Harvard Medical School
Alexander S. Banks: Beth Israel Deaconess Medical Center and Harvard Medical School
Francesca Raffin: Beth Israel Deaconess Medical Center and Division of Sleep Medicine and Program in Neuroscience, Harvard Medical School
Oscar D. Ramirez-Plascencia: Beth Israel Deaconess Medical Center and Division of Sleep Medicine and Program in Neuroscience, Harvard Medical School
Sydney Aten: Beth Israel Deaconess Medical Center and Division of Sleep Medicine and Program in Neuroscience, Harvard Medical School
Janayna D. Lima: Beth Israel Deaconess Medical Center and Division of Sleep Medicine and Program in Neuroscience, Harvard Medical School
Sathyajit S. Bandaru: Beth Israel Deaconess Medical Center and Division of Sleep Medicine and Program in Neuroscience, Harvard Medical School
Richard D. Palmiter: University of Washington
Clifford B. Saper: Beth Israel Deaconess Medical Center and Division of Sleep Medicine and Program in Neuroscience, Harvard Medical School

Nature, 2025, vol. 644, issue 8076, 463-472

Abstract: Abstract Many species use a temporary decrease in body temperature and metabolic rate (torpor) as a strategy to survive food scarcity in a cool environment. Torpor is caused by preoptic neurons that express a variety of peptides and receptors1–7, but no single genetic marker has been found for this population. Here we report that expression of the prostaglandin EP3 receptor (EP3R) marks a unique population of median preoptic nucleus (MnPO) neurons that are required for both torpor and lipopolysaccharide-induced fever8. The MnPO-EP3R neurons produce persistent fever responses when inhibited and prolonged hypothermic responses when activated either chemogenetically or optogenetically, even for brief periods of time. The mechanism for these prolonged responses appears to involve increases in intracellular levels of cAMP and calcium that may persist for many minutes up to hours beyond the termination of a stimulus. These properties endow the population of MnPO-EP3R neurons with the ability to act as a two-way switch for the hypothermic and hyperthermic responses that are required for survival.

Date: 2025
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DOI: 10.1038/s41586-025-09056-1

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