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

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Vollmar,  Stefan
Vollmar – IT and Software Development, Scientific Services and Development, Max Planck Institute for Metabolism Research, Max Planck Society;

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Fenselau,  Henning
Fenselau – Synaptic Transmission in Energy Homeostasis, Research Groups, Max Planck Institute for Metabolism Research, Max Planck Society;

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Wunderlich,  Frank T.
Wunderlich – Obesity and Cancer, Department Brüning, Max Planck Institute for Metabolism Research, Max Planck Society;

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Brüning,  Jens C.
Brüning – Neuronal Control of Metabolism, Department Brüning, Max Planck Institute for Metabolism Research, Max Planck Society;

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Citation

Biglari, N., Gaziano, I., Schumacher, J., Radermacher, J., Paeger, L., Klemm, P., et al. (2021). Functionally distinct POMC-expressing neuron subpopulations in hypothalamus revealed by intersectional targeting. Nature neuroscience, (7), 913-929.


Cite as: https://hdl.handle.net/21.11116/0000-000C-7609-6
Abstract
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.