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Publication : Functionally distinct POMC-expressing neuron subpopulations in hypothalamus revealed by intersectional targeting.

First Author  Biglari N Year  2021
Journal  Nat Neurosci Volume  24
Issue  7 Pages  913-929
PubMed ID  34002087 Mgi Jnum  J:314806
Mgi Id  MGI:6726771 Doi  10.1038/s41593-021-00854-0
Citation  Biglari N, et al. (2021) Functionally distinct POMC-expressing neuron subpopulations in hypothalamus revealed by intersectional targeting. Nat Neurosci 24(7):913-929
abstractText  Pro-opiomelanocortin (POMC)-expressing neurons in the arcuate nucleus of the hypothalamus represent key regulators of metabolic homeostasis. Electrophysiological and single-cell sequencing experiments have revealed a remarkable degree of heterogeneity of these neurons. However, the exact molecular basis and functional consequences of this heterogeneity have not yet been addressed. Here, we have developed new mouse models in which intersectional Cre/Dre-dependent recombination allowed for successful labeling, translational profiling and functional characterization of distinct POMC neurons expressing the leptin receptor (Lepr) and glucagon like peptide 1 receptor (Glp1r). Our experiments reveal that POMC(Lepr+) and POMC(Glp1r+) neurons represent largely nonoverlapping subpopulations with distinct basic electrophysiological properties. They exhibit a specific anatomical distribution within the arcuate nucleus and differentially express receptors for energy-state communicating hormones and neurotransmitters. Finally, we identify a differential ability of these subpopulations to suppress feeding. Collectively, we reveal a notably distinct functional microarchitecture of critical metabolism-regulatory neurons.
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