Prostaglandin EP3 receptor-expressing preoptic neurons bidirectionally control body temperature via tonic GABAergic signaling

The bidirectional controller of the thermoregulatory center in the preoptic area (POA) is unknown. Using rats, here, we identify prostaglandin EP3 receptor-expressing POA neurons (POAEP3R neurons) as a pivotal bidirec-tional controller in the central thermoregulatory mechanism. POAEP3R neurons are activated in response to el-evated ambient temperature but inhibited by prostaglandin E2, a pyrogenic mediator. Chemogenetic stimulation of POAEP3R neurons at room temperature reduces body temperature by enhancing heat dissipation, whereas inhibition of them elicits hyperthermia involving brown fat thermogenesis, mimicking fever. POAEP3R neurons innervate sympathoexcitatory neurons in the dorsomedial hypothalamus (DMH) via tonic (ceaseless) inhibitory signaling. Although many POAEP3R neuronal cell bodies express a glutamatergic messenger RNA marker, their axons in the DMH predominantly release gamma-aminobutyric acid (GABA), and their GABAergic termi-nals are increased by chronic heat exposure. These findings demonstrate that tonic GABAergic inhibitory sig-naling from POAEP3R neurons is a fundamental determinant of body temperature for thermal homeostasis and fever.

Automated summary

In this study, the bidirectional control of the thermoregulatory center in the preoptic area (POA) was investigated using rats. Prostaglandin EP3 receptor-expressing POA neurons (POAEP3R neurons) were identified as a pivotal bidirectional controller in the central thermoregulatory mechanism. These neurons are activated in response to elevated ambient temperature but inhibited by prostaglandin E2. Stimulation of these neurons reduces body temperature by enhancing heat dissipation, while inhibition of them leads to hyperthermia involving brown fat thermogenesis.