Genetic identification of preoptic neurons that regulate body temperature in mice

There has been an explosion recently in our understanding of the neuronal populations in the preoptic area involved in thermoregulation of mice. Recent studies have identified several genetically specified populations of neurons predominantly in the median preoptic nucleus (MnPO) but spreading caudolaterally into the preoptic area that regulate body temperature. . These include warm-responsive neurons that express the peptides PACAP, BDNF, or QRFP; and receptors for temperature, leptin, estrogen, or prostaglandin E2 (PGE2). These neurons are predominantly glutamatergic and driving them opto- or chemogenetically can cause profound hypothermia, and in some cases, periods of torpor or a hibernation-like state. Conversely, fever response is likely to depend upon inhibiting the activity of these neurons through the PGE2 receptor EP3. Another cell group, the Brs3-expressing MnPO neurons, are apparently cold-responsive and cause increases in body temperature. MnPO-QRFP neurons cause hypothermia via activation of their terminals in the region of the dorsomedial nucleus of the hypothalamus (DMH). As the MnPO-QRFP neurons are essentially glutamatergic, and the DMH largely uses glutamatergic projections to the raphe pallidus to increase body temperature, this model suggests the existence of local inhibitory interneurons in the DMH region between the MnPO-QRFP glutamatergic neurons that cause hypothermia and the DMH glutamatergic neurons that cause hyperthermia. The new genetically targeted studies in mice provide a way to identify the precise neuronal circuitry that is responsible for our physiological observations in this species, and will suggest critical experiments that can be undertaken to compare these with the thermoregulatory circuitry in other species.