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dc.contributor.authorSaucisse, Nicolas
dc.contributor.authorMazier, Wilfrid
dc.contributor.authorSimon, Vincent
dc.contributor.authorBinder, Elke
dc.contributor.authorCatania, Caterina
dc.contributor.authorBellocchio, Luigi
dc.contributor.authorRomanov, Roman A
dc.contributor.authorLéon, Stéphane
dc.contributor.authorMatias, Isabelle
dc.contributor.authorZizzari, Philippe
dc.contributor.authorQuarta, Carmelo
dc.contributor.authorCannich, Astrid
dc.contributor.authorMeece, Kana
dc.contributor.authorGonzales, Delphine
dc.contributor.authorClark, Samantha
dc.contributor.authorBecker, Julia M
dc.contributor.authorYeo, Giles SH
dc.contributor.authorFioramonti, Xavier
dc.contributor.authorMerkle, Florian
dc.contributor.authorWardlaw, Sharon L
dc.contributor.authorHarkany, Tibor
dc.contributor.authorMassa, Federico
dc.contributor.authorMarsicano, Giovanni
dc.contributor.authorCota, Daniela
dc.date.accessioned2022-01-07T00:31:01Z
dc.date.available2022-01-07T00:31:01Z
dc.date.issued2021-10-12
dc.identifier.issn2211-1247
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332252
dc.description.abstractHypothalamic pro-opiomelanocortin (POMC) neurons are known to trigger satiety. However, these neuronal cells encompass heterogeneous subpopulations that release γ-aminobutyric acid (GABA), glutamate, or both neurotransmitters, whose functions are poorly defined. Using conditional mutagenesis and chemogenetics, we show that blockade of the energy sensor mechanistic target of rapamycin complex 1 (mTORC1) in POMC neurons causes hyperphagia by mimicking a cellular negative energy state. This is associated with decreased POMC-derived anorexigenic α-melanocyte-stimulating hormone and recruitment of POMC/GABAergic neurotransmission, which is restrained by cannabinoid type 1 receptor signaling. Electrophysiology and optogenetic studies further reveal that pharmacological blockade of mTORC1 simultaneously activates POMC/GABAergic neurons and inhibits POMC/glutamatergic ones, implying that the functional specificity of these subpopulations relies on mTORC1 activity. Finally, POMC neurons with different neurotransmitter profiles possess specific molecular signatures and spatial distribution. Altogether, these findings suggest that mTORC1 orchestrates the activity of distinct POMC neurons subpopulations to regulate feeding behavior.
dc.format.mediumPrint
dc.publisherElsevier BV
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectCB(1) receptor
dc.subjectEndocannabinoid
dc.subjectFood intake
dc.subjectGABA
dc.subjectGlutamate
dc.subjectMelanocortin
dc.subjectPOMC neuron
dc.subjectmTOR
dc.titleFunctional heterogeneity of POMC neurons relies on mTORC1 signaling.
dc.typeArticle
dc.publisher.departmentDepartment of Clinical Biochemistry
dc.date.updated2022-01-05T16:52:08Z
prism.issueIdentifier2
prism.numberARTN 109800
prism.publicationDate2021
prism.publicationNameCell Rep
prism.startingPage109800
prism.volume37
dc.identifier.doi10.17863/CAM.79697
dcterms.dateAccepted2021-09-15
rioxxterms.versionofrecord10.1016/j.celrep.2021.109800
rioxxterms.versionVoR
dc.contributor.orcidMerkle, Florian [0000-0002-8513-2998]
dc.identifier.eissn2211-1247
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (211221/Z/18/Z)
pubs.funder-project-idMRC (MR/P501967/1)
pubs.funder-project-idMedical Research Council (MC_UU_12012/1)
pubs.funder-project-idMedical Research Council (MC_UU_12012/5)
pubs.funder-project-idMRC (MR/S026193/1)
pubs.funder-project-idMRC (MC_UU_00014/1)
pubs.funder-project-idMRC (MC_UU_00014/5)
cam.depositDate2022-01-05
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International