1531-P: Identification of a Novel Subset of Cold-Activated Hypothalamic Neurons That Stimulate Feeding

Growing evidence suggests that the hypothalamus plays an important role in the coupling of thermoregulation to energy homeostasis. Based on preliminary evidence that neurons expressing tyrosine hydroxylase (TH) located in the rostral hypothalamus are activated by cold exposure, we sought in the current work to 1) map this previously unrecognized neural subpopulation and, 2) investigate its role(s) in the control of food intake. To this end, four groups of C57Bl6 mice were studied. Two of the groups either exposed to a cold (10 °C) or a warm environment (30 °C) for 90 min, while the other two were either fasted overnight or fed ad libitum (AL). Brains were then processed for immunohistochemical colocalization of cFos, a marker of neuronal activation, in TH(+) neurons. Our findings reveal that relative to mice housed in a warm environment, cold exposure increased the % of TH neurons expressing fos selectively in the periventricular hypothalamic nucleus (Pe) (22.5 ± 1.2% for cold vs. 5.0 ± 1.3% for warm, a ~4-fold increase; p<0.001). In contrast, cFos was not detectably induced in TH(+) neurons located in the caudal PVN (p=ns). Overnight fasting had a similar effect to increase the % of Pe^TH neurons expressing cFos (26.0 ± 3.8% for fast vs. 13.4 ± 2.5% for fed, a ~2-fold increase; p<0.05), but again was without effect in caudal PVN^TH neurons. To determine whether activation of Pe^TH neurons is sufficient to increase food intake, TH-Cre animals received a unilateral microinjection of a Cre-inducible excitatory DREADD receptor directed to this brain area. Here, we found that relative to vehicle-treated controls, food intake was robustly increased following CNO-induced activation of Pe^TH neurons (0.94 ± 0.18g with CNO vs. 0.28 ± 0.09g with vehicle, a ~3-fold increase; p<0.01). These findings implicate a novel set of cold-activated hypothalamic TH neurons in the regulation of food intake.