RRC ID 56695
Author Wang TA, Teo CF, Åkerblom M, Chen C, Tynan-La Fontaine M, Greiner VJ, Diaz A, McManus MT, Jan YN, Jan LY.
Title Thermoregulation via Temperature-Dependent PGD2 Production in Mouse Preoptic Area.
Journal Neuron
Abstract Body temperature control is essential for survival. In mammals, thermoregulation is mediated by the preoptic area of anterior hypothalamus (POA), with ∼30% of its neurons sensitive to brain temperature change. It is still unknown whether and how these temperature-sensitive neurons are involved in thermoregulation, because for eight decades they have only been identified via electrophysiological recording. By combining single-cell RNA-seq with whole-cell patch-clamp recordings, we identified Ptgds as a genetic marker for temperature-sensitive POA neurons. Then, we demonstrated these neurons' role in thermoregulation via chemogenetics. Given that Ptgds encodes the enzyme that synthesizes prostaglandin D2 (PGD2), we further explored its role in thermoregulation. Our study revealed that rising temperature of POA alters the activity of Ptgds-expressing neurons so as to increase PGD2 production. PGD2 activates its receptor DP1 and excites downstream neurons in the ventral medial preoptic area (vMPO) that mediates body temperature decrease, a negative feedback loop for thermoregulation.
Volume 103(2)
Pages 309-322.e7
Published 2019-7-17
DOI 10.1016/j.neuron.2019.04.035
PII S0896-6273(19)30392-7
PMID 31151773
PMC PMC6639135
MeSH Action Potentials / drug effects Action Potentials / physiology Animals Body Temperature / drug effects Body Temperature / physiology Body Temperature Regulation / genetics Body Temperature Regulation / physiology* CRISPR-Associated Protein 9 / genetics CRISPR-Associated Protein 9 / metabolism Clozapine / pharmacology Dinoprostone / genetics Dinoprostone / metabolism Excitatory Amino Acid Antagonists / pharmacology Gene Expression Regulation / genetics HEK293 Cells Humans Locomotion / drug effects Locomotion / genetics Male Mice Mice, Inbred C57BL Mice, Transgenic Neurons / drug effects Neurons / physiology* Preoptic Area / cytology* Preoptic Area / drug effects Preoptic Area / physiology* Prostaglandin D2 / genetics Prostaglandin D2 / metabolism* Temperature*
IF 14.403
Times Cited 6
Mice RBRC01868