Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenaline

The arcuate nucleus of the hypothalamus (ARH) is one key structure controlling energy homeostasis. While it has been shown that the biogenic amines dopamine and serotonin modulate food intake controlling NPY/AgRP and/or POMC neurons in the ARH, the neural substrates that mediate the effect of noradrenaline (NA) on energy homeostasis remain elusive. By electrophysiological recordings and cell type-specific transcriptomics we show that the main neuronal populations in the ARH, NPY/AgRP and POMC neurons express a combination of excitatory and inhibitory adrenergic receptors (ARs). Surprisingly, NA had a clear differential effect on these neurons. Activation of NPY/AgRP neurons is mediated by _1A - and _- ARs, while POMC neurons are inhibited via _2A ARs. Collectively, our data indicate an orexigenic influence of NA on the ARH circuitry that controls energy balance Overall design: We have isolated NPY- and POMC-expressing neuronal populations by means of FACS-sorting green fluorescent protein expressed under the Npy or Pomc gene promoter, from the hypothalami of 6-week-old mice. We have extracted total RNA and prepared libraries from these samples, sequenced and identified differentially expressed genes between the two neuronal populations, in order to identify in an unbiased way, which and how agrenergic receptor genes are differentially expressed under these conditions.