摘要It has been shown that prostaglandin(PG)E2 synthesized in the lateral parabrachial nucleus(LPBN)is involved in lipopolysaccharide-induced fever.But the neural mechanisms of how intra-LPBN PGE2 induces fever remain unclear.In this study,we investigated whether the LPBN-preoptic area(POA)pathway,the thermoafferent pathway for feed-forward thermoregulatory responses,mediates fever induced by intra-LPBN PGE2 in male rats.The core temperature(Tcore)was monitored using a temperature radiotelemetry transponder implanted in rat abdomen.We showed that microinjection of PGE2(0.28 nmol)into the LPBN significantly enhanced the density of c-Fos-positive neurons in the median preoptic area(MnPO).The chemical lesioning of MnPO with ibotenate or selective genetic lesioning or inhibition of the LPBN-MnPO pathway significantly attenuated fever induced by intra-LPBN injection of PGE2.We demonstrated that EP3 receptor was a pivotal receptor for PGE2-induced fever,since microinjection of EP3 receptor agonist sulprostone(0.2 nmol)or EP3 receptor antagonist L-798106(2 nmol)into the LPBN mimicked or weakened the pyrogenic action of LPBN PGE2,respectively,but this was not the case for EP4 and EP1 receptors.Whole-cell recording from acute LPBN slices revealed that the majority of MnPO-projecting neurons originating from the external lateral(el)and dorsal(d)LPBN were excited and inhibited,respectively,by PGE2 perfusion,initiating heat-gain and heat-loss mechanisms.The amplitude but not the frequency of spontaneous and miniature glutamatergic excitatory postsynaptic currents(sEPSCs and mEPSCs)in MnPO-projecting LPBel neurons increased after perfusion with PGE2;whereas the frequency and amplitude of spontaneous inhibitory postsynaptic currents(sIPSCs)and the A-type potassium(IA)current density did not change.In MnPO-projecting LPBd neurons,neither sEPSCs nor sIPSCs responded to PGE2;however,the IA current density was significantly increased by PGE2 perfusion.These electrophysiological responses and the thermoeffector reactions to intra-LPBN PGE2 injection,including increased brown adipose tissue thermogenesis,shivering,and decreased heat dissipation,were all abolished by L-798106,and mimicked by sulprostone.These results suggest that the pyrogenic effects of intra-LPBN PGE2 are mediated by both the inhibition of the LPBd-POA pathway through the EP3 receptor-mediated activation of IA currents and the activation of the LPBel-POA pathway through the selective enhancement of glutamatergic synaptic transmission via EP3 receptors.