Activity of preoptic area neurons supports thermal effector activation during fever

Prostaglandin E2 (PGE2) in the preoptic area (POA) mimics fever by stimulating thermogenesis in brown adipose tissue (BAT), skeletal muscle via shivering and the heart via tachycardia, as well as by reducing heat loss via skin vasoconstriction. PGE2-evoked stimulations of BAT, shivering EMGs and heart rate (HR) are postulated to arise from disinhibition of thermogenesis-promoting neurons in the dorsomedial hypothalamus (DMH), and possibly in the rostral raphe pallidus (rRPa), due to the EP3 receptor (EP3-R)-mediated inhibition of GABAergic, warm-sensitive neurons in the POA that project to inhibit DMH (and possibly rRPa) neurons. We tested the hypothesis that neurons in the medial preoptic (MPO) provide the necessary excitatory drive to downstream, thermogenesis-promoting neurons for febrile heat production. Bilateral muscimol injection in the MPO completely inhibited the shivering EMGs and reversed the increases in BAT temperature and HR following injection of PGE2 into the POA. We conclude that the MPO contains neurons whose activity is necessary to support thermogenesis during fever. The data are consistent with a model in which a population of MPO neurons provides a tonically-active, excitatory (glutamatergic) input to DMH (and rRPa?) neurons that drives thermogenesis upon disinhibition of DMH neurons during EP3-R activation in the POA and potentially during cold exposure. Support NIH grant NS40987.