Neuronal Responses to Melatonin in Peromyscus leucopus: A Candidate Mechanism for Circadian and Seasonal Temperature Regulation

Melatonin, a hormone secreted by the pineal gland, relays information about the current day length (photoperiod) to various target tissues. The melatonin signal can be used to predict the coming season, and thus the probable environmental conditions, in order to initiate appropriate physiological and behavioral adjustments. Melatonin can also regulate certain outputs of the circadian pacemaker, including sleep and body temperature. Despite decades o f research on the many putative functions of melatonin, their underlying neural basis remains poorly understood. We chose to investigate the possible mechanisms by which melatonin affects core body temperature (T b ) . A number o f studies indicate a role for melatonin in seasonal and circadian changes in Tb, including a decline in Tb in short photoperiods in rodents, and a modest influence on the circadian temperature rhythm in humans. A plausible site for the thermoregulatory action of melatonin is the preoptic area and anterior hypothalamus (PO/AH). According to a well-supported model of hypothalamic temperature control, a substance can adjust the set-point of Tb by differentially altering the firing rates of warmsensitive and temperature-insensitive neurons in the PO/AH. To test whether melatonin can act upon the PO/AH in this manner, we performed in vitro electrophysiological recordings during melatonin treatment, using a white-footed mouse (.Peromyscus leucopus) tissue slice preparation. A secondary hypothesis was that populations of white-footed mice exhibit individual variation in neuronal sensitivity to temperature and melatonin. Reproductive responsiveness to photoperiod is highly variable in this species, but it is not known whether photoresponsiveness generalizes to non-reproductive functions, such as thermoregulation. To approach this question, we compared responses to melatonin and temperature in mice from two lines selected for reproductive photoresponsiveness. Our results provide the first evidence for a direct effect of melatonin on thermoregulatory neurons in the hypothalamus, but more data are needed to confirm whether responses to melatonin are correlated with neuronal thermosensitivity. Small differences were found between photoresponsive and non-photoresponsive mice, but low sample sizes limit the conclusions we can make from these data. Nevertheless, our characterization and mapping of melatoninand temperature-sensitive neurons will facilitate future research in this area. NEURONAL RESPONSES TO MELATONIN IN PEROMYSCUS LEUCOPUS