2. Academic Validation
  3. Preoptic EP3R neurons constitute a two-way switch for fever and torpor

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

  • Nature. 2025 May 28. doi: 10.1038/s41586-025-09056-1.
Natalia L S Machado 1,  Nicole Lynch 2,  Luis H A Costa 2 3,  David Melville 2,  Hakan Kucukdereli 4,  Satvinder Kaur 2,  Alexander S Banks 4,  Francesca Raffin 2 5,  Oscar D Ramirez-Plascencia 2,  Sydney Aten 2,  Janayna D Lima 2,  Sathyajit S Bandaru 2,  Richard D Palmiter 6,  Clifford B Saper 7
Affiliations

Affiliations

  • 1 Department of Neurology, Beth Israel Deaconess Medical Center and Division of Sleep Medicine and Program in Neuroscience, Harvard Medical School, Boston, MA, USA. nmachado@bidmc.harvard.edu.
  • 2 Department of Neurology, Beth Israel Deaconess Medical Center and Division of Sleep Medicine and Program in Neuroscience, Harvard Medical School, Boston, MA, USA.
  • 3 School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
  • 4 Division of Endocrinology, Metabolism and Diabetes, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
  • 5 Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Pavia, Italy.
  • 6 Howard Hughes Medical Institute and Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • 7 Department of Neurology, Beth Israel Deaconess Medical Center and Division of Sleep Medicine and Program in Neuroscience, Harvard Medical School, Boston, MA, USA. csaper@bidmc.harvard.edu.
PMID: 40437091 DOI: 10.1038/s41586-025-09056-1
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.

Figures
Products