TY - JOUR TI - Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenalin AU - Paeger, Lars AU - Karakasilioti, Ismene AU - Altmüller, Janine AU - Frommolt, Peter AU - Brüning, Jens AU - Kloppenburg, Peter A2 - Elmquist, Joel K VL - 6 PY - 2017 DA - 2017/06/20 SP - e25770 C1 - eLife 2017;6:e25770 DO - 10.7554/eLife.25770 UR - https://doi.org/10.7554/eLife.25770 AB - In the arcuate nucleus of the hypothalamus (ARH) satiety signaling (anorexigenic) pro-opiomelanocortin (POMC)-expressing and hunger signaling (orexigenic) agouti-related peptide (AgRP)-expressing neurons are key components of the neuronal circuits that control food intake and energy homeostasis. Here, we assessed whether the catecholamine noradrenalin directly modulates the activity of these neurons in mice. Perforated patch clamp recordings showed that noradrenalin changes the activity of these functionally antagonistic neurons in opposite ways, increasing the activity of the orexigenic NPY/AgRP neurons and decreasing the activity of the anorexigenic POMC neurons. Cell type-specific transcriptomics and pharmacological experiments revealed that the opposing effect on these neurons is mediated by the activation of excitatory α1A - and β- adrenergic receptors in NPY/AgRP neurons, while POMC neurons are inhibited via α2A – adrenergic receptors. Thus, the coordinated differential modulation of the key hypothalamic neurons in control of energy homeostasis assigns noradrenalin an important role to promote feeding. KW - noradrenalin KW - neuromodulation KW - AgRP-neuron KW - POMC-neuron JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -